Chapter 15 - Compounding 1: Basics Flashcards

Question

SCA

Answer 1

Segregated Compounding Area Designated space that contains ISO 5 hood but is not part of the clean room

Answer 2

Secondary Engineering Control ISO 7 buffer room where Sterile room PEC is located

Answer 3

Small Volume Parenteral IV bag or container containing s; 100 ml

Answer 4

- 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).

Answer 5

- Primary engineering control (PEC, called the sterile hood, or isolator, if using a glove box) - 3520

Answer 6

Not applicable (ISO 6 is not used for pharmacy spaces) 35,200 m3

Answer 7

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

Answer 8

Anteroom, if it opens into a positive pressure SEC 3,520,000 m3

Answer 9

- 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.

Answer 10

- 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.

Answer 11

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.

Answer 12

- 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.

Answer 13

- 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.

Answer 14

■ 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.

Answer 15

- 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.

Answer 16

- 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).

Answer 17

- 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.

Answer 18

- 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.

Answer 19

- 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).

Answer 20

- 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.

Answer 21

- 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 and Other Hazardous Drugs in Healthcare Settings. - 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 ■ Labeled by the manufacturer with special handling instructions

Answer 22

1) Abortifacient - Mifepristone - Misoprostol 2) Antibiotics - Chloramphenicol 3) Anticoagulants - Warfarin 4) Antifungals - Fluconazole, - Voriconazole 5) Antiretrovirals - Abacavir - Entecavir - Zidovudine 6) Antivirals - Cidofovir - Ganciclovir - Valganciclovir 7) Acne - lsotretinoin 8) Arrhythmias - Dronedarone 9) Autoimmune Conditions - Acitretin - Azathioprine - Leflunomide - Fingolimod - Teriflunomide

Answer 23

1) Benign Prostatic Hyperplasia (BPH) - Dutasteride - Finasteride 2) Bisphosphonates - Pamidronate - Zoledronic Acid 1) Chemoprotectant (Cardiac) - Dexrazoxane 1) Depression - Paroxetine 2) Diabetes - Exenatide, - Liraglutide 3) Dyslipidemia - Lomitapide

Answer 24

1) Seizures/Epilepsy - Clobazam - Clonazepam - Carbamazepine - Oxcarbazepine - Eslicarbazepine - Divalproex - Fosphenytoin - Phenytoin - Topiramate - Vigabatrin - Zonisamide 1) Gout - Colchicine

Answer 25

1) Heart Failure - lvabradine - Spironolactone 1) Hepatitis - Ribavirin 2) Hormonal Agents - Androgens (e.g.,testosterone) - Estrogens (e.g.,estradiol) - Oxytocin - Dinoprostone - Progesterones (e.g.,medroxyprogesterone) - SERD/SERMs (e.g.,fulvestrant, tamoxifen) - Ulipristal 3) Hyperthyroidism - Methimazole - Propylthiouracil

Answer 26

1) Insomnia - Temazepam - Triazolam 2) Iron Overload - Deferiprone 1) Migraine - Dihydroergotamine

Answer 27

1) Parkinson Disease - Apomorphine - Rasagiline 2) Pulmonary Arterial Hypertension (PAH) - Ambrisentan - Bosentan - Macitentan - Riociguat

Answer 28

1) Schizophrenia - Ziprasidone 1) Transplant - Cyclosporine - Mycophenolate - Tacrolimus - Sirolimus

Answer 29

- 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: ■ Personal protective equipment (PPE) ■ First aid procedures ■ Spill clean-up procedures

Answer 30

- 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 - 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.

Answer 31

Risk is defined differently in USP 797 and 800: 1) USP 797 risk categories are based on risk of contamination of the sterile product. 2) With hazardous drug compounding (USP 800), higher risk means a higher chance of causing harm to the workers exposed to the drug . - The USP 800 requirements for safe handling of HDs are extensive, but some activities are not as risky as others. - Some examples of lower-risk activities include counting and packaging tablets. - A pharmacy can conduct an ASSESSMENT of RISK (AoR) for drugs with lower risk to avoid having to follow all USP 800 requirements for drugs that will be dispensed without manipulation. - If any manipulation of the low-risk hazardous drug is required (e.g., using powder to prepare a solution, cutting tablets in half, adding a vial of HD to a large volume fluid), USP 800 requirements must be followed. - If no AoR is conducted, the pharmacy must follow the full USP 800 requirements. - AoR documents must be reviewed at least every 12 months and the review must be documented.

Answer 32

■ Putting HDs in distinctive shelf bins to alert staff ■ Wearing ASTM D6978-rated gloves when counting or packaging drugs ■ Dedicating a counting tray and spatula for counting HDs and decontaminating both after use ■ Placing prepared HD containers into a sealable plastic bag

Answer 33

Hoods and buffer rooms used for compounding HDs include the word containment: ■ Containment-primary engineering control (C-PEC) ■ Containment-secondary engineering control (C-SEC) ■ Containment-segregated compounding area (C-SCA) ■ Compounding aseptic containment isolator (CACI) Containment is required to keep hazardous drugs, particles and vapors contained within the space due to toxicity risk.

Answer 34

- Both sterile and non-sterile hazardous compounds must be prepared in a C-PEC that is located in a C-SEC or C-SCA. Types of C-PECs are listed below. ■ Biological safety cabinets (BSCs): - Have vertical laminar airflow (air flows down from the HEPA filter at the top of the hood) and - Negative air pressure, which protects the worker from being exposed to the hazardous drug they are working with. - For sterile hazardous drug compounding, the BSC must be Class II (most common) or Class III. ■ Containment ventilated enclosures (CVEs): - Are powder containment hoods with HEPA-filtered air - negative air pressure used for non-sterile compounding only. ■ Compounding aseptic containment isolators (CACis) - Are closed-front C-PECs (glove boxes) - Can be located in a buffer room (SEC), - But are often located in a C-SCA.

Answer 35

- While it is preferable to keep non-sterile and sterile compounding space separate, an exception can be made to prepare non-sterile hazardous drugs in a C-PEC inside a C-SEC, if these requirements are met: ■ The C-SEC must maintain ISO 7 air even when it is being used for non-sterile HD compounding. ■ If there are separate sterile and non-sterile C-PECs in the same C-SEC, they must be kept at least 1meter apart. ■ Particle-generating activity, such as working with powders, cannot be performed when any sterile compounding is being performed in the same C-SEC. ■ Occasional non-sterile HD compounding can be completed in a sterile C-PEC, but it must be properly decontaminated, cleaned and disinfected before using again to compound sterile HDs.

Answer 36

C-PECs, C-SECs and C-SCAs must have negative air pressure. ■ Negative air pressure in the C-PEC causes the air to flow into the C-PEC (away from the person who is standing at the front of the hood), and then to flow out of the C-PEC through the external exhaust at the top of the hood. ■ Negative air pressure in the C-SEC keeps air from flowing into the anteroom. It is removed through the room exhaust.

Answer 37

- Air in spaces used for HD compounding can get contaminated and needs to be regularly replaced. - The air changes per hour (ACPH) is the number of times (per hour) that the air is replaced in the room. ■ In space where non-sterile HDs are compounded there must be at least 12 ACPH. ■ In a sterile C-SEC there must be at least 30 ACPH. This requirement also applies to a sterile SEC for non-HDs. ■ In a C-SCA there must be at least 12 ACPH.

Answer 38

- Air that has been contaminated with HDs must be externally exhausted. - This means that the air is moved out of the space (from the C-PEC, from the C-SEC or from the non-sterile HD compounding space) and cannot be recirculated and returned to the room. - It is sent outside and takes any contamination out with it.

Answer 39

- Community pharmacies can be located in areas that would not welcome contaminated air exhaust, such as a compounding pharmacy that prepares HDs that is located adjacent to a busy park. - An alternative option to an external exhaust (for non-sterile HD compounding only) is to use redundant HEPA filters. - Air is passed through two or more HEPA filters in a series

Answer 40

Hazardous drugs must be stored separately from non- hazardous drugs in an externally ventilated, negative- pressure room with at least 12 ACPH

Answer 41

Personnel (i.e., staff) must have proper training for each type of compounding they perform. All training must be documented. ■ Initial training includes: - Didactic training (teaching, with lectures or videos) & - Hands-on training (compounding), - Must be observed by the designated person in charge of compounding (i.e., compounding supervisor) or a staff expert. ■ Continuous (ongoing) training must also be completed. - When work is new or different for any reason, the compounding staff must receive additional training. - This can include new drugs, revised drug information, changes in equipment and new or revised procedures.

Answer 42

Staff must demonstrate that they can follow adequate aseptic procedures for each of these items prior to independently compounding sterile products: ■ Hand hygiene ■ Garbing and gloving technique ■ Cleaning and disinfecting procedures for the sterile space and equipment ■ Sterile drug preparation Adequate aseptic technique in hand hygiene, garbing and gloving is demonstrated by passing the gloved fingertip test. Adequate aseptic technique in sterile drug preparation is demonstrated by passing the media-fill test.

Answer 43

- A passing score on the gloved fingertip test is required initially, then annually (if compounding only low- and medium-risk CSPs) or semi-annually (if compounding high- risk CSPs). - The evaluator collects a gloved sample from each hand of the compounder by rolling the pads of the fingers and thumb over a surface which contains tryptic soy agar (TSA). If microorganisms are present, they will use the TSA as a food source and replicate. The plates are incubated (heated, to facilitate growth) for 2 - 3 days and then inspected for microbial growth, which will be visible as spots on the plates. Spots that form are called colony-forming units (CFUs) and indicate contamination was present on the gloves

Answer 44

■ Initial test: passing requires three consecutive gloved fingertip samples, taken after garbing, with zero CFUs for both hands. ■ Ongoing competency: at least one sample taken from each hand immediately after completion of the media-fill test, with a goal of~ 3 CFUs total for both hands.

Answer 45

- The media-fill test is used to determine if a compounder is preparing CSPs in an aseptic manner. - The test must be performed initially during training and at least annually for low- and medium-risk level compounding and semiannually for high-risk compounding. - Tryptic soy broth (TSB) takes the place of the drug in the preparation. - TSB is a growth medium used by the organisms to replicate. - A small IV bag or vial can be used for the test. - Multiple aseptic manipulations (transfers using the same syringe) are done and then the product is incubated and checked for bacterial growth. - Turbidity (cloudiness) means contamination is present. - If the liquid stays clear after 14 days of incubation, the compounder passed the test.

Answer 46

- Temperatures must be kept in the appropriate range and documented on the temperature log sheet (see clipboard). - The SEC (buffer room) should be checked once daily and be maintained at 20°C (68°F), or cooler. - The refrigerator and freezer should be monitored daily unless they contain vaccines, which require twice daily monitoring. - The refrigerator temperature should be between 2- 8°C. If a freezer contains only CSPs (no vaccines), then the freezer temperature should be between -25 and-10°C, according to USP797. - If the freezer also contains vaccines, the required freezer temperature is -50 to -15°C per CDC guidance. * If the temperature is out of range, action must be taken and documented .

Answer 47

ensure that the environment for compounding sterile products is acceptably free of contaminants.

Answer 48

Air sampling identifies contaminants in the air. It should be performed at least every 6 months by a person certified in air sampling, or by a qualified compounding staff member.

Answer 49

- USP requires that surfaces be tested periodically. - Tryptic soy agar (TSA) provides a good growth medium. - Polysorbate 80 and lecithin are added to the TSA to neutralize the effect of any disinfecting agents on the surfaces. - The testing should occur at the end of the day when the surfaces are in the poorest state. - All surfaces that are regularly exposed to staff (e.g., inside the PECs and other work surfaces, door handles, equipment) should be tested. - At least one surface sample must be taken from each ISO 5, 7 and 8 area. - After the plates have been incubated for 2 - 3 days, the results should indicate zero CFUs (preferred). - Action must be taken if > 3 CFUs are identified in the ISO 5 area, > 5 CFUs in the ISO 7 area and > 100 CFUs in the ISO 8 area. - If action is needed, polymerase chain reaction (PCR) can be used to identify the microorganisms present, which can help determine the source (e.g.,Staphylococci are likely from the compounding staff; Pseudomonas can be due to water condensation from poor air conditioning or personnel contamination

Answer 50

Air pressure testing confirms there is the correct differential (difference in pressures) between two spaces and ensures that the airflow is unidirectional (i.e., in one direction out from or into a space). - Pressure gauges are installed in the cleanroom space, and checked (minimally) once daily or with every work shift.

Answer 51

- Humidity must be carefully controlled to prevent the presence of excess moisture in the sterile compounding area, which can lead to bacterial growth. - The humidity should be below 60% and should be checked at least once daily.

Answer 52

At least every 6 months Goals: Vary based on ISO level; immediate action required for highly pathogenic organisms (e.g.,Gram-negative rods, molds and yeasts)

Answer 53

Periodically Goal is zero CFUs; action must be taken if: ■ >3CFUs in the ISO5area >5 CFUs in the ISO7 area or > 100 CFUs in the ISO 8 area ■ Any growth of highly pathogenic organisms

Answer 54

Each shift (preferably) or daily (minimally) goal: Non-hazardous cleanroom: positive Hazardous cleanroom: negative

Answer 55

daily goal: < 60 %

Answer 56

- All PECs and C-PECs are preferably kept running at all times to help keep the surfaces clean. - If there is a power outage, all compounding must stop, and the PECs will need to be cleaned with a germicidal detergent and then disinfected - If the PEC is a C-PEC, sanitization will be needed if the power has been turned off. The sanitization process is more complex, and is described on the following page. - If the power has been off, in addition to cleaning and disinfecting (or sanitization for C-PECs), the PEC or C-PEC must be on for at least 30 minutes before compounding can begin.

Answer 57

- The PECis cleaned throughout the day (see below), and at the end of the day it is cleaned again (first) before cleaning the SEC and the anteroom. - Lint-free sterile wipes are used to clean the PEC. - First, the PECis cleaned with a germicidal detergent, then disinfected with 70% IPA. - There are wipes that come pre-soaked with the appropriate agent. - Alternatively, a spray bottle can be used to wet a dry wipe. - Never spray inside the PEC. - Use slightly overlapping, unidirectional strokes rather than circular motions. - Use a new side of the wipe for the next area cleaned, and replace used wipes often. - PECs are cleaned from top to bottom, back to front. This means that the cleanest areas will be cleaned first, and the dirtiest areas will be cleaned last.

Answer 58

This is an example of the order of cleaning for a PEC. 1. Clean the ceiling of the hood, from back to front. 2. Clean the grill over the HEPA filter, from top to bottom. 3. Clean the side walls starting from back to front, wiping up and down in a long sweeping motion. Clean the IV bar and hooks. Either the side walls or the bar can be cleaned first. 4. Clean anything kept in the hood [e.g., automated compounding device (used for parenteral nutrition), or other equipment]. 5. Clean the bottom surface (the work area) starting from back to front, with a side to side motion. Do not start compounding until the surfaces have dried.

Answer 59

1) All Sterile Work: - Before entering the cleanroom, wipe the outside container of all supplies. - Clean with germicidal cleaner and disinfect with sterile 70% IPA, every day: counters, floors & carts 2) For Hazardous Drugs: - Always sanitize the work area at the end of a shift: Deactivate, Decontaminate, Clean, Disinfect - Leaving HD residue for the next shift is NOT acceptable and is likely a justification for termination

Answer 60

Ceiling Walls Shelving Chairs Bins Carts

Answer 61

- Before each shift - Every 30 minutes while working - Before and after each batch of CSPs - Whenever needed. including after spills

Answer 62

- All areas and equipment used for handling HDs must be sanitized, which includes deactivating, decontaminating and cleaning at least once daily. - Sterile compounding areas and equipment must be disinfected as a final step. - It is important to perform the sanitizing steps in the correct order; if the disinfecting step is done before deactivating, it will spread the HD residue. - When using the sanitizing agents, wetted wipes should be used instead of using a spray bottle to directly spray onto the surfaces and equipment. - This is because the spray can cause any HD residue to aerosolize and spread to other areas. - All workers performing these activities must wear appropriate PPE. - A NIOSH approved fit-tested respirator should be used if the sash of the BSC or the front cover of the CACI is opened. - There are several commercially available kits which simplify the sanitization process, and multi-purpose agents that combine deactivation and decontamination, such as Peridox RTU. - Bleach or peroxide can be used for both steps. - Bleach can cause corrosion on stainless steel surfaces, which includes the surfaces of C-PECs. - To prevent corrosion, neutralize the bleach by wiping surfaces afterwards with sodium thiosulfate, sterile alcohol, sterile water or a germicidal detergent. - All areas where HDs are handled (receiving, transporting, compounding, administering, disposal), reusable equipment and devices must be routinely deactivated/decontaminated and cleaned. - The cleaning and disinfecting schedule from USP 800 applies to both sterile and non-sterile HD compounding areas. Decontamination is required anytime a spill occurs.

Answer 63

2% Bleach (Sodium Hypochlorite) or Peroxide Reduce HD toxicity, then remove HD residues

Answer 64

Germicidal Detergent, such as Quat, Ammonium Phenolics Removes dirt and microbial contamination

Answer 65

Sterile 70% lsopropyl Alcohol (IPA) Inhibits or destroys microorganisms; required step in sterile compounding

Answer 66

Pharmacies involved in hazardous compounding should perform wipe sampling of all compounding surfaces initially and at least every 6 months to ensure that hazardous residue is adequately contained. Areas in the C-PEC, C-SEC and anteroom should be tested for contamination. If contamination is present, the designated individual must identify the source and implement a plan to contain it.

Answer 67

The most urgent action to take when a staff member has an exposure (whether to a non-HD, a chemical in the workplace or a HD) is to get the drug or chemical off the person as soon as possible. - The first 10 to 15 seconds after exposure are critical. Delaying treatment, even for a few seconds, may cause serious injury. - Protocols for emergency procedures should be kept in the pharmacy. Minimal actions to take: 1. For an exposure to gloves or gown, immediately remove the garb that has the drug on it. 2. Immediately cleanse any affected skin with soap and water. 3. For an eye exposure, flood the affected eye at an eyewash fountain (see image above), or with water or an isotonic eyewash for at least 15 minutes. Depending on the chemical, the time required for flushing can be longer. 4. Obtain medical attention, when warranted. 5. Document the exposure in the employee's record.

Answer 68

- Remove any HD exposed to the skin as soon as possible. Emergency medical treatment must be sought with significant skin exposure and with mucus membrane and inhalation exposure. - Chemotherapeutics and some other HDs can irritate the eyes and mucus membranes in the nose and mouth and cause lung damage. - Eye and face protection must be worn when there is a risk for HDs pills or splashes, including when working in a PEC and when working outside of a PEC (e.g., when administering the drug to a patient or cleaning up a spill). - Goggles are used for eye protection. - Eye glasses alone or safety glasses with side shields do not protect the eyes adequately from splashes; face shields in combination with goggles is preferable and provides complete protection against splashes to the face and eyes.

Answer 69

When HDs are unpacked and they are not contained in plastic, the staff member should wear an elastomeric half-mask, with a multi-gas cartridge and PlO0-filter, until assessment of the packaging integrity ensures that no breakage or spillage occurred during transport. An N95 respirator is sufficient for most HD compounding, but does not provide adequate protection against gases, vapors or direct liquid splashes.

Answer 70

■ Cleaning up spills that need more supplies to clean up than provided by a spill kit. ■ Deactivating, decontaminating and cleaning underneath the work surface of a C-PEC. ■ When there is a known or suspected airborne exposure to HDpowders or vapors. ■ Disposal of PPE used when handling HDs, which will be contaminated with (minimally) trace amounts. When there is a risk of respiratory exposure, one of the following should be worn: ■ A fit-tested respirator mask with attached gas canisters (a "gas mask"); see picture below on the left. ■ A powered air-purifying respirator (PAPR)that blows air through the filter to the user (see picture above on the right). PAPRsare easier to breathe through than the gas mask type but require a fully charged battery to work properly. They use the same filters as gas masks.

Answer 71

- HD spills must be cleaned up immediately. - Depending on the facility, all of the compounding staff can be trained to handle HD spills, or the facility can have a trained spill response team. - The Safety Data Sheet (SDS) should be consulted for guidance on spill clean-up procedures.

Answer 72

■ Who refers to the staff who will respond to assist with people exposed to the spill and who will respond to clean up the spill. If HD exposure has occurred, emergency medical help will be needed. ■ What refers to the rapid assessment of the situation to determine if additional help will be needed. ■ When refers to the urgent need to clean up hazardous spills immediately.

Answer 73

■ Spill kits for HDs must be kept in areas where HDs are prepared, stored and administered. The spill kits must be available immediately wherever HDs travel, which is where they can spill. ■ Quickly limit access to the area, and post warning signs around the perimeter of the spill. Multiple signs can be needed if more than one entry opens into the area with the spill. Pregnant women should not be involved with any clean-up activities and should immediately leave the area. ■ The warning sign should state Caution:HazardousSpill, Proceedwith Care!or something similar.

Answer 74

■ Protective gown, latex gloves (minimally), N95 respirator mask plus~ with side shields ■ HD waste bag, scoop and scraper to get spill waste into the waste bag, chemo pads to absorb hazardous liquid ■ HDspill report exposure form to document HDexposure

Answer 75

- Open the spill kit. - The PPE should be donned immediately to protect the staff cleaning up the spill. ■ Put the heavy-duty gloves over the ASTM D6978 (chemotherapy)-rated gloves, which are the type used for HD compounding. The heavy-duty gloves protect the hands from broken glass. ■ Clean up macro amounts (big amounts) of spilled drug and broken glass. - Never use a brush to clean up broken glass and powder that is contaminated with HDs. Brushes can cause particles to become airborne. ■ If liquid is present, cover the liquid with an absorbent spill pad. ■ Next, decontaminate the surfaces on which the HD has spilled from the area of lesser contamination to areas of greater contamination to avoid spreading the hazard. ■ If moistened pads are not available, pour the solution on the pads. Do not spray. ■ Put trash into a hazardous waste bag, and seal. This is bulk hazardous waste, which is discarded in the black bulk hazardous waste bin.

Answer 76

■ Doff (remove}garb and perform hand hygiene. ■ Decontaminate the respirator and replace the cartridges. ■ Replace the spill kit.

Answer 77

Black Is for Bulk HD waste: any containers (drug vials, IV bags)that contain a clearly visible amount of HD and any supplies that were used to administer HDs or to clean up HD spills.

Answer 78

Yellow is for Trace HD waste empty syringes, IV bags, used PPE, including gowns, gloves, masks & shoe covers.

Answer 79

No! The red waste bin is for infectious waste, including IV tubing & used culture dishes The red sharps container is only for non-hazardous sharps, such as used syringes. The used syringes from preparing HDs go into the yellow bin.

Answer 80

Appropriate PPE must be worn when administering HDs. Two pairs of chemotherapy gloves are required when administering all HDs. A chemotherapy gown is required when administering IV HDs and recommended when administering other HDs (e.g.,oral} Closed-system drug transfer devices (CSTDs}must be used by nurses for drug administration, if available for the formulation being used. Chemotherapy pins are used to prevent HDsfrom aerosolizing by reducing air pressure with venting. They can be used during reconstitution and during administration. The pins attach with a luer lock connection, CSTDs should be used to transfer drugs whenever possible to keep the HDs contained within the device. CSTDs reduce leaks and spills when withdrawing solutions from vials, injecting solutions into IV bags, reconstituting dried powders into solutions and for syringe to syringe transfers. CSTDs are recommended when compounding HDs and required for administering antineoplastics, if available. CSTDs have a built-in valve that equalizes the air pressure when fluid is added or withdrawn from the vial Pharmacy and nursing should try to avoid manipulating oral HDs, such as crushing tablets and opening capsules. If a liquid formulation of the drug is available, it should be used. If manipulation is required (e.g., crushing tablets) it should be done in a plastic bag to contain any dust or particles.

Answer 81

All PPE worn when handling HDs are considered contaminated with trace amounts. The outer chemotherapy gloves worn during compounding are discarded in a yellow trace chemotherapy waste bin located inside the C-PECor put in a sealable bag if discarding outside the C-PEC.Remove the outer glove before handling and labeling the compounded preparation. The chemotherapy gown and outer shoe covers must be taken off before exiting the negative-pressure area and thrown away in the yellow trace chemotherapy waste bin. The rest of the garb is removed when leaving the ante- room or C-SCAonce the compounding session is complete All trace antineoplastic waste (i.e., empty vials, empty syringes, empty IV bags, IV tubes, used gloves, used gowns, used pads) is thrown away in a yellow container, which will be destroyed by incineration (burning) at a waste facility. Bulk antineoplastic waste, which includes unused or partially empty IV bags, syringes and vials, are thrown away in a black container, which will be incinerated at a waste facility.

Answer 82

When HDs need to be transported, they must be properly labeled and packaged to minimize the risk of spillage or breakage. - Pneumatic tube systems cannot be used to transport any liquid HDs or any antineoplastics because of the potential for breakage and contamination.

Answer 83

Garb attire includes hair covers (bonnets), beard covers, special shoes or shoe covers, gowns, gloves, face masks, eye shields and aprons. The garb attire required depends on the type of compounding performed. The staff have to be protected from chemical exposure (some drugs are more toxic than others), and the drug needs to be protected from contamination. Hand hygiene and garbing is more detailed for sterile compounding.

Answer 84

Appropriate PPE must be worn with each step involving HDs: receiving, storage, transporting, compounding (sterile and non-sterile), administration, sanitation and during spill control. - Double ASTM D6978 (chemotherapy)-rated gloves are required when compounding or cleaning up spills. - Single gloves can be used for HD receiving and storage.

Answer 85

Placing intact tablets or capsules into unit-dose or multidose containers on an occasional basis poses relatively low risk to the healthcare worker. A single pair of gloves may be adequate. When USP 800 is not being followed completely (which requires 2 pairs of gloves), it must be based on anAoR that has identified the drugs which can have less stringent requirements, and the procedures put in place to reduce risk. Repeatedly counting, cutting or crushing tablets poses a higher risk for worker exposure and contamination to the workplace if exposure controls are not in place. If a BSCor CACIis not available, then PPE should be used that includes: ■ Double gloves, a gown, a mask and ■ A disposable pad to protect the work surface

Answer 86

PPEfor sterile hazardous drug compounding includes: ■ Head covers, a face mask and (if applicable) beard covers ■ Twopairsofshoecovers ■ Agownimpermeable toliquids ■ Two pairs of ASTMD6978(chemotherapy)-rated gloves ■ A full-facepiece respirator or a face shield with goggles when there is a risk for spills or splashes The following pages illustrate how to don garb for sterile compounding, followedby requirements for sterile hazardous garb. Removing coats, sweaters, makeup and visible jewelry is required before entering the ante-area. Some pharmacies have compounders change into scrubs at work; these may be cleaner than street clothes, and are light and comfortable. The scrubs are laundered and kept on site to decrease the flow of microbes from the outside.

Answer 87

■ Remove coats, rings, watches, bracelets and makeup before entering the ante-area. Artificial or long nails are not permitted. ■ No make-up is permitted because it sheds. ■ Don head and facial hair covers and face masks, then shoe covers while stepping over the line of demarcation that separates the dirty side of the anteroom from the clean side. A second pair of shoe covers are needed for compounding HDs. The ante-area should have a mirror that is used to check that the hair is completely covered. An eye shield is optional, except if preparing a hazardous drug. ■ Perform hand hygiene with soap and warm water. Most contamination of CSPs comes from the hands. ■ Under warm water, clean under fingernails to remove debris. ■ Working from the fingertips to the elbows, wash vigorously in circular motions for 30 seconds. ■ Dry hands and forearms with lint-free disposable towels. ■ Don a non-shedding gown that fits snugly around the wrists and has an enclosure at the neck. Disposable gowns are required for HD compounding and preferred for non-HD compounding. If gowns are reusable, they must be laundered prior to reuse. ■ Enter the buffer area (SEC). ■ Apply an alcohol-based surgical hand scrub with persistent antimicrobial activity for the recommended amount of time (per manufacturer) and allow to dry. The FDA has issued a warning for serious allergic reactions to chlorhexidine, which many compounders use. Another option is povidone- iodine (Betadine). which can be used if there has been an allergic reaction to chlorhexidine. ■ Don sterile, powder-free gloves. Two pairs of ASTM D6978 (chemotherapy)-rated gloves are required for compounding HDs. Tuck one pair under the cuffs of the gown. The second pair goes over the cuffs. ■ Sanitize the gloves with 70% IPA routinely during compounding and whenever the gloves touch non-sterile surfaces. Do not resume compounding until the alcohol has dried. Continually inspect gloves for tears. ■ All garb must be used when compounding with an isolator (glove box) unless the isolator's manufacturer provides written documentation that garb is not required. ■ When the compounding is completed and the compounding personnel leaves the cleanroom/compounding area, all garb except for the gown goes into the disposal container. If the gown is not visibly soiled, it can be taken off and kept on the clean side of the anteroom in order to be re-worn for the current work shift. The gown cannot leave the ante area if it is going to be re-worn. Hand hygiene is repeated, and all other garb is replaced when re-entering the compounding area.

Answer 88

■ Garb should not be worn outside of the anteroom; if the anteroom has been exited, complete regarbing is required, including hand hygiene. ■ If working in an SCA and it is left for any reason, regarbing is required.

Answer 89

Garb is donned in the ante area. The order in which the garb should be donned is from dirtiest to cleanest. 1) Respirator - A fit tested NIOSH-certified N95 respirator is appropriate for most activities that need respiratory protection. - A surgical respirator provides the respiratory protection of an N95 respirator, and provides the protection of a surgical mask. - An elastomeric half-mask with a multi-gas cartridge and P100-filter should be used for unpacking HDs which are not wrapped in plastic. - A full-face piece, chemical cartridge-type respirator or powered air-purifying respirator (PAPR)should be worn for cleaning up large HD spills, sanitizing the under tray of a C-PEC, or when there is a known or suspected airborne exposure to powders or vapors. 2) FaceMask - Required for sterile compounding 3) Head and Hair Covers 4) Eye/FaceProtection - Must be worn when there is a risk for HD spills or HD splashes when working outside of a C-PEC. - A full-face piece respirator or a face shield with goggles is acceptable. 5) Chemotherapy Gloves - Must meet the American Society for Testing and Materials (ASTM) standard D6978 (or its successor). Powder-free. - Must not have pin holes or weak spots. - Must be changed every 30 minutes or when torn, punctured or contaminated. - Two pairs must be worn while administering chemotherapy drugs and while compounding sterile and higher-risk non-sterile HDs. - For low-risk non-sterile HDs, such as intact tablets, one pair of gloves is acceptable. - When two pairs of gloves are worn with a gown, one pair should go under the cuff of the gown and the other pair should go over the cuff of the gown. 6) ChemotherapyGown - Must be disposable (may not be reused). - Must be impermeable; polyethylene-coated polypropylene or other laminate material is best. - Must close in the back, be~ sleeved. and have closed cuffs (elastic or knit). - No seams or closures that can trap HD particles. - Must be changed per manufacturer's schedule, or if unknown, change every 2-3 hours or immediately after a spill or splash. - Disposable sleeve covers made of coated materials can be used with the gown. 7) Shoe Covers Two pairs are required when compounding sterile HDs.