Compounding & Hazardous Drugs PDF

COMPOUNDING & HAZARDOUS DRUGS r-:~ CHAPTER 15 COMPOUNDING I: BASICS WHAT ARE COMPOUNDED DRUGS? 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. Compo...

COMPOUNDING & HAZARDOUS DRUGS r-:~ CHAPTER 15 COMPOUNDING I: BASICS WHAT ARE COMPOUNDED DRUGS? 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. THE DIFFERENT TYPES OF COMPOUNDING Compounded drugs are either non-sterile or sterile. Both non-sterile and sterile compounded drugs can be further subdivided into two categories: non-hazardous and hazardous (see diagram on next page). 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). COMPOUNDING STANDARDS AND RESOURCES U.S. Pharmacopeia The U.S. Pharmacopeia (USP) sets the standards for compounding preparations. The USP Chapters related to compounding include USP 795 (Non-Sterile Compounding), USP 797 (Sterile Compounding) and USP 800 (Handling Hazardous Dl'ugs). USP does not determine which drugs are hazardous; it simply sets the requirements for safe handling of hazardous drugs (HDs). USP 795, 797 and 800 are considered to be minimum acceptable standards for compounding by the Food and Drug Administration (FDA), the state boards of pharmacy and the Joint Commission. USP standards apply to all who engage in compounding (pharmacy staff, nurses and physicians), and all practice settings (hospitals, other healthcare institutions, clinics and pharmacies). 232 RxPREP 2022 COURS E BO OK I RxPRE P ©202 1, © 202 2 Compounding Non-Sterile Sterile (e.g., orals, topicals, nasals) (e.g., IV drugs, eye drops) l Non-Sterile l Non-Hazardous Nott-Hazardous USP795 USP797 USP795 and 800 ..Q. Sterlle Sterile Huardous l USP 797 and 800 ; ~imxPrep !U:J Standard Studio/Shutterstock.com USP 795 divides non-sterile compounding into three categories based on complexity: USP Compounding Chapters A phannacopeia is a list of medicinal drugs, with preparation instructions. 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) The U.S. Pharmacopeia (USP) _,,_,, sets standards for preparation, strength, quality and purity of human and animal drugs, including manufactured and compounded drugs. 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) In June 2019, USP published revisions to chapters 795 and 797. They are currently under appeal and have not yet been finalized. The current versions of USP 795 (2014) and USP 797 (2008) remain official until further notice from USP. American Society of Health-System Pharmacists Hospital pharmacists rely on the American Society of Health-System Pharmacists (ASHP) for detailed guidance on implementing USP standards, NON-STERILE COMPOUNDING Non-sterile compounding is primarily used to: Prepare a dose or formulation that is not commercially available, such as: o Changing a solid tablet to a liquid for a patient who cannot swallow the tablet o Compounding a 10% ointment when only 5% and 15% are available Avoid au 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 EI mouth, via tube, rectally, vaginally. topically, nasally 01· in the ear. Complex: requires specialized training, equipment, facilities or procedures (e.g., transdermal dosage forms) 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 tl1e 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. 233 15 I CO MPOUNDIN G I: BAS ICS STERILE COMPOUNDING Sterile compounding must be carried out using strict procedures to keep products free from contamination. 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: • Intravenous (IV) drugs (e.g., 1 gram of vancomycin taken from a vial and injected into a 250 mL DSW IV bag) • lntramusculai• (IM) and subcutaneous (SC, SQ) drugs Radiopharmaceuticals (nuclear medicine drugs) • Eye drops (e.g., moxifloxacin and prednisolone eye drops) Please garb in PPE for HD CSPs. You will be working in, . , ~ h e BSC in the C-SEC today. - . -:7" • -e v Say what? Irrigations (liquid "washes" that go into a body cavity, such as a gentamicin bladder irrigation) • Pulmonary inhalations (does not include nasal inhalations) Before getting into the details, review the terminology used by USP, which is provided in the Study Tip Gal below. MEANING COMMON TERMS BSC Biological Safety Cabinet Cherne hood (Class II or Ill for sterile HD), a type of C-PEC CACI Compounding Aseptic Containment Isolator "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 HDs C-SCA Containment Segregated Compounding Area Ventilated (negative pressure) room used for H Os; not in a clean room 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 H Os if USP 800 standards are met) LAFW Laminar Airflow Workbench Type of sterile hood (PEC); parallel air streams flow in one direction lVP large Volume Parenteral IV bag or container containing> 100 ml PEC Primary Engineering Control 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 hood (includes CAls and CACls) SCA Segregated Compounding Area Designated space that contains an ISO 5 hood but is not part of a cleanroom suite (air is not ISO-rated) SEC Secondary Engineering Control ISO 7 "buffer room" where the sterile hood (PEC) is located SVP Small Volume Parenteral IV bag or container containing~ 100 ml ---I I - I L 234 I Sterile hood that provides ISO 5 air for compounding _, RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 USP 797 SPACE REQUIREMENTS FOR STERILE COMPOUNDING There are greater (and stricter) compounding space requirements for sterile compounding than non-sterile compounding. AIR QUALITY AND HEPA FILTERS Clean air in the compounding area reduces the risk of contamination. 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 dosest to exposed sterile drugs and containers [i.e., 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 ISO 7. 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). COMPOUNDING AREA ISO RATING Primary engineering control (PEC, called the sterile hood, or isolator, if using a glove box) 5 Not applicable (ISO 6 is not used for pharmacy spaces) ____ 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) Anteroom, if it opens into a positive pressure SEC J 6 7 PARTICLES/m 3 ------7 - ~ 3,520 35,200 1 352,000 _________, 8 3,520,000 High-Efficiency Particulate Air Filters 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. In a vertical airflow biological safety cabinet (BSC) or C-PEC, the HEPA filter is at the top of the sterile hood. In a laminar airflow workbench (LAFW) or PEC, the HEPA filter is at the back of the sterile hood (horizontal airflow). 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 (see the Study Tip Gal on the following page). The HEPA filter must be recertified by a specialist every 6 months and anytime a PEC has been moved. 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. V:X-.:X-111'.ll:..:W~~llC.m:ar::::JUC: Ambient (room) air is ~ISO 9, with 35 million particles per cubic meter 235 15 I COMPOUNDING I: BASICS PHYSICAL SPACE BASICS The Direct Compounding Area and First Air 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 during compounding, the injection port of the vial and the syringe needle must be kept in the first air (see image). Do not obstruct first air, especially the area where the needle enters the vial or ampule. 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. r Do not block airflow from the HEPA filter with hands or supplies. Place items correctly inside the PEC (see the Compounding Ill chapter) to avoid creating turbulence, which can lead to contamination of the CSPs. Prevent Contamination by Keeping the Air in the PEC Clean Wipe off the outside of all materials (e.g., 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. Most contamination to CSPs comes from the compounding staff, largely from inadequate hand hygiene and garbing; correct l_t ~c~'li~ e is essential, and is described later in this chapter. AIR PRESSURE In addition to the ISO air quality in a space, the air pressure in the space relative to the adjacent space is important. 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 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 a.i..L1low 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. There must be a differential (i.e., a 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. Room Air . . . FIitered Air Horizontal laminar airflow 236 RxPREP 2022 COURSE BOOK 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). Positive air pressure from the work area through the antechamber (where the staff move Items In and out) protects the CSPs, C) = oo I RxPREP ©2021, ©2022 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. Handwashing and donning of the gown occur on the clean side of the anteroom. Compounded Sterile Products Needed Stat The requirements described in this chapter for compounding sterile products, including putting on protective garb and cleaning the PEC (described later), 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 beyonduse date (BUD) of 1 hour, after which the drug can no longer be used and must be discarded. BUDs are described in the Compounding III chapter. SEGREGATED COMPOUNDING AREA 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. CSP risk categories are discussed further in the Compounding III chapter. 1i, 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. 1h11 waste buckets are red, for sharps and_ non-hazardous waste, ;ti .___ _ _ _ _ _ _ _ _ _ __ ____ _ _ _ ___, Compounding Aseptic Isolator SECONDARY ENGINEERING CONTROL The SEC is the room that contains the PEC or multiple PECs. The SEC is commonly called the buffer area or buffer room because it provides a "buffer" of relatively clean air (ISO 7) around the PEC (ISO 5). 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). ANTEROOM 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 CAI in a Segregated Compounding Area 237 15 I COMPOUNDING I: BASICS POSITIVE PRESSURE NON-HAZARDOUS DRUG CLEANROOM Secondary Engineering Control (SEC) Primary Engineering Control (PEC) The SEC is the room that contains the PEC, called a "buffer room" because it provides a buffer of relatively clean air (ISO 7) around the PEC. Types of PECs: Horizontal laminar airflow workbench (LAFW), as shown in image Compounding aseptic isolator (CAI), more commonly seen in a SCA outside of a cleanroom "First air" into the direct compounding area (DCA) is the cleanest. Do not block airflow with hands or supplies and work at least six inches from the front edge. Positive air pressure in the PEC and SEC protects the CSPs from contamination. When the door is opened, air will flow out of the SEC and into the adjacent anteroom. Anteroom For non-hazardous drug compounding, the anteroom can be ISO 7 or 8. Positive air pressure means the dirtier ISO 8 air will not blow into the SEC and risk contaminating the CSPs. ll:l3 ©RxPrep 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. THE NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH The National Institute for Occupational Safety and Health (NIOSH) determines which drugs are hazardous. NIOSH keeps a list of all HDs called the NIOSH List of Anti neoplastic ana Other Hazantous Drugs in Healthcare Settings (see Key Drugs Guy on the following page). HDs should be handled according to USP 800 requirements. A drugs is considered hazardous if it is: • Carcinogenic (cancer-causing) Teratogenic (causes congenital disabilities) or reproductive toxicity (e.g., infertility) • Genotoxic (damages DNA, which can cause cancer) Toxic to organs at low doses 238 • Labeled by the manufacturer with special handling instructions RxPREP 20 22 COUR SE BOOK Antlneoplastlc Drugs (Chemotherapeutics) Non-Antlneoplastic Hazardous Drugs on the NIOSH List Abortlfacient Mifepristone, Misoprostol Antibiotics Chloramphenicol Anticoagulants Warfarin Antlfungals Fluconazole, Voriconazole Antiretrovirals Abacavir, Entecavir, Zidovudine Antivirals Cidofovir, Ganciclovir, Valganciclovir Acne lsotretinoin Arrhythmias I RxPREP Benign Prostatlc Hyperplasia (BPH) Hormonal Agents Dutasteride, Finasteride Androgens (e.g., testosterone) Bisphosphonates © 20 2 1, © 20 22 Estrogens (e.g., estradiol) Pamidronate, Zoledronic Acid Chemoprotectant (Cardiac) Dexrazoxane Oxytocin, Dinoprostone Progesterones (e.g., medroxyprogesterone) SERD/SERMs (e.g., fulvestrant, tamoxifen) Depression Paroxetine Ulipristal Diabetes Hyperthyroidism Exenatide, Liraglutide Methimazole, Propylthiouracil Dysllpldemia Insomnia Lomita pi de Temazepam, Triazolam Seizures/Epilepsy Iron Overload Clobazam, Clonazepam Deferiprone Carbamazepine, Oxcarbazepine, Eslicarbazepine, Divalproex, Fosphenytoin, Phenytoin, Topiramate, Vigabatrin, Zonisamide Migraine Dihydroergotamine Parkinson Disease Apomorphine, Rasagiline Gout Pulmonary Arterial Hypertension (PAH) Colchicine Heart Failure Ambrisentan, Bosentan, Macitentan, Riociguat Autoimmune Conditions lvabradine, Spironolactone Acitretin, Azathioprine, Leflunomide Schizophrenia Hepatitis Ziprasidone Ribavirin Transplant Dronedarone Fingolimod, Teriflunomide Cyclosporine, Mycophenolate, Tacrolimus, Sirolimus SAFETY DATA SHEETS (SDS) HAZARD COMMUNICATION PROGRAM SDS (previously called MSDS) are a series of safety documents required by the Occupational Safety and Health Administration (OSHA) to be accessible to all employees who are working with hazardous materials, including drugs. Each hazardous drug has its own document, which provides guidance on drug-specific safety information including: Each facility must have a designated individual who is responsible for creating Standard Operating Procedures (SOPs) focused on worker safety during all aspects of hazardous drug handling. This hazard communication program includes a written plan that details implementation of HD safety procedures, proper training of personnel, competency assessment and maintaining all required HD documentation. Pharmacies must maintain a list of all hazardous drugs stocked. The list must be reviewed every 12 months or whenever a new drug or dosage form is stocked or used. Prior to handling any HDs, both men and women with reproductive capability (the ability to have children) must confirm in writing that they understand the risks associated with handling HDs. Personal protective equipment (PPE) First aid procedures Spill clean-up procedures 239