Hazardous Drug Compounding Cleaning & Risk Assessment PDF

15 I COM POUNDIN G I: BASI CS ASSESSING RISK FOR HAZARDOUS DRUGS Risk is defined differently in USP 797 and 800. USP 797 risk categories are based on risk of contamination of the sterile product. With hazardous drug compounding (USP 800), higher risk means a higher chance of causing harm to the w...

15 I COM POUNDIN G I: BASI CS ASSESSING RISK FOR HAZARDOUS DRUGS Risk is defined differently in USP 797 and 800. USP 797 risk categories are based on risk of contamination of the sterile product. 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. As part of the AoR, SOPs must be developed, which include actions to limit staff exposure, such as: 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 C-PECs for Hazardous Drug Compounding 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 and negative air pressure used for non-sterile compounding only. Compounding aseptic containment isolators (CACfs} are closed-front C-PECs (gloveboxes) that can be located in a buffer room (SEC), but are often located in a C-SCA. Compounding Aseptic Containment Isolator (CACI) EXTERNAL VENT The Isolator for compounding HDs will contain hazardous fumes/particles, which will be vented externally. Neptlve air pressure from the work area through the antechamber keeps the HD fumes/particles away from the compounding staff when items are passed In and out. t Placing prepared HD containers into a sealable plastic bag 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. 00 USP 800 SPACE REQUIREMENTS PHYSICAL SPACE BASICS 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. 240 _ _ _ ___. i\'J] Compounding Aseptic Containment Isolator RxPREP 2022 CO URSE BOOK Non-Sterile and Sterile HD Compounding in the Same Space 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 1 meter 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. External Exhaust Redundant HEPA Filters Instead of External Exhaust 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 (see the illustration below}. f 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. Air Changes 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. ©2021, ©2022 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 cannotbe recirculated and returned to the room. It is sent outside and takes any contamination out with it. AIR HANDLING FOR HAZARDOUS DRUGS C-PECs, C-SECs and C-SCAs must have negative air pressure. I RxPREP Double-Filtered Air FAN I [ HEPA FIiter #1 l ~ J J_ I I l l ~EP~Fll~!~ I' L. L ,,,-; Negative Press~ / I / II I .,_ @ ~ - - -- - - -- - - - - - - - - ~ (q Redundant HEPA Filters HAZARDOUS DRUG STORAGE Hazardous drugs must be stored separately from nonhazardous drugs in an externally ventilated, negativepressure room with 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. 241 15 I CO MP O UND I NG I : BASI CS NEGATIVE PRESSURE HAZARDOUS DRUG CLEANROOM Containment Primary Engineering Control (C-PEC) Types of C-PECS: Containment Secondary Engineering Control (C-SEC) Biological safety cabinet (pictured) Air changes per hour (ACPH) in the C-SEC must be: Compounding aseptic containment isolator (CACI, can be used in a C-SCA) 2: 12 for non-sterile compounding Negative air pressure in the C-PEC and C-SEC protects the compounding staff by removing hazardous contaminants and sending them outside. Anteroom For sterile hazardous drug com pounding, the anteroom must be ISO 7. Negative air pressure means the air will blow into the SEC and risk contaminating the CSPs. @©RxPreµ ------- 242 Rx PREP 20 2 2 COURSE BOOK I RxPREP © 2021, © 20 22 • Initial training includes didactic training (teaching, with lectures or videos) and hands-on training (compounding), which must be observed by the designated person in charge of compounding (i.e., compounding supervisor) or a staff expert. If microorganisms are present, they will use u the TSA as a food source a "t ., and replicate. The plates ::,: .2 are incubated (heated, to <lJ facilitate growth) for 2 - 3 "' :, days and then inspected for cl microbial growth, which \Q will be visible as spots on Gloved Fingertip Test the plates. Spots that form are called colony-forming units (CFUs) and indicate contamination was present on the gloves. • 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. Passing a Gloved Fingertip Test Initial test: passing reguiI'es three consecutive gloved fingertip samples, taken after garbing, with zero CFUs for both hands. COMPOUNDING STAFF TRAINING Personnel (i.e., staff) must have proper training for each type of compounding they perform. All training must be documented. 0 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. REQUIRED TRAINING AND TESTING FOR STERILE COMPOUNDING 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 m.edia-f1ll test. GLOVED FINGERTIP TEST 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 highrisk CSPs). The evaluator collects a gloved sample from each hand of the com pounder by rolling the pads of the fingers and thumb over a surface which contains t1·yptic soy agar (TSA). ~- 1 I I I - MEDIA-FILL TEST 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-1'isk 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. Passing a Media-Fill Test If the liquid stays clear after 14 days of incubation, the compounder passed the test. Media Fill Test ---No, you need to have 3 consecutive tests with ZERO growth. You have lots of bacteria growing. Those s p o t s , . , are called colony forming units (CFUs). Your hands were contaminated! ,,,.. Plus, you failed your other test! You introduced contamination during the work process. '$ e- 1-iowdoyou know that? fl!+ Do you remember we did the media-fill test the last time you compounded sterile products? We filled up some small IV bags that contained tryptic soy broth (TSB) and sent them to incubate. We were t e s t i ~ g for growth that was introduced while you ,.. were compounding. ,. W Well, there was growth. • 243 15 I COMPO U N D ING I: BASICS TEMPERATURE MONITORING 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 coole1•. 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 USP 797. 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. It feels hot in the SEC. I hope the CSPs are okay. Would you please check that the temperature is not above 68°F (or 20°C)? Thanks. Pharmacy TEMPERATURE Log Form PH-246 ONCE Daily 1 Date I TWICE Daily SECRoom Vacdne Refrigerator Vaccine Freezer s:20°c 2-s•c -so-1s c S:68°F 36-46°F ·58-5°F 0 2/1 ---+-----+ 2/2 2/3 2/4 2/5 2/6 2/7 2/8 ... end of month fl;lJ <1,".!RxPrep AIR AND SURFACE TESTING In addition to personnel testing with the gloved fingertip test and the media-fill test, there are other tests that are used to ensure that the environment for compounding sterile products is acceptably free of contaminants. AIR SAMPLING 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. 244 RxPREP 2022 COURSE BOOK SURFACE SAMPLING 0 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 r"1 t) RxProp 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). ( I RxPREP ©2021, ©2022 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). AIR PRESSURE TESTING 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. HUMIDITY CONTROL 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. Alrsampllng At least every 6 months Vary based on ISO level; immediate actionf'equired for highly pathogenic organisms (e.g. Gram-negative rods, molds and yeasts) Surface sampling Perlodlcally Goal is zero CFUs; action must be taken if: > 3 CFUs in the ISO 5 area > 5 CFUs In the ISO 7 area or > 100 CFUs in the ISO 8 area Any growth of highly pathogenic organisms ..., E 8 LL'. Air pressure Each shift (preferably) or dally (mlnlmally) Non-hazardous deanroom: positive Hazardous cleanroom: negative "',.., lu >- Humidity Dally (minimally) " <60% >- "<: a" lffi ©RxPrep 245 15 I COMPOUND I NG I: BASICS KEEPING THE STERILE COMPOUNDING AREA CLEAN KEEP THE PEC RUNNING 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 with sterile 70% isopropyl alcohol (lPA) prior to re-initiation of compounding activity. 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. CLEAN THE PEC CONTINUOUSLY The PEC is 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 PEC is 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 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 than circular motions. Use a new side of the wipe for the next area cleaned, and replace used wipes often. PECs are cleaned from !QI?. to bottom, back to front. This means that the cleanest areas will be cleaned first, and the dirtiest areas will be cleaned last. Cleaning a Horizontal Laminar Airflow PEC 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. 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 ,/ Before each shift Clean side walls and work surface from back to front in long sweeps. Walls Shelving Chairs Bins Carts I ,/ Every 30 minutes while working ,/ Before and after each batch of CSPs ,/ Whenever needed, including after spills rm @RxPrep 246 ......':.:.:.:.:.:.:.:.:.:.:.-:.=.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.-::.:.:.:.::.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.E.=...---~~- Rx PR EP 2022 COURSE BOO K HAZARDOUS DRUG COMPOUNDING CLEANING SPECIFICS SANITIZATION 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. I RxPREP ©2021. ©2022 I like these different colored waste bins. What goes in the black waste bin? r-:~ Black is for Bulk HD waste: , . , any containers (drug vials, IV _ bags) that contain a clearly -a .visible amount of HD and any supplies that were used to administer HDs or to clean up HD spills. DEACTIVATION and DECONTAMINATION 2% Bleach (Sodium Hypochlorite) or Peroxide What goes in the yellow waste bin? Reduce HD toxicity, then remove HD residues CLEANING Germicidal Detergent, such as Quat, Ammonium, Phenolics Removes dirt and microbial contamination . Yellow is for Trace HD waste: , . , empty syringes, IV bags, used PPE, including gowns, gloves, masks & shoe covers, '9 -;j" DISINFECTION Sterile 70% lsopropyl Alcohol (IPA) Inhibits or destroys microorganisms; required step In sterile compounding 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. Are you saying that I don't throw the used syringes I use for the chemo drugs Into the red waste bin? No! The red waste bin is for infectious waste, including IV tubing and 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, SURFACE SAMPLING FOR HAZARDOUS DRUGS 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. 247