Isolators

 When asepsis is not required, a Class I Biological Safety Cabinet (BSC) or a containment isolator may be used to handle hazardous drugs.  When sterile hazardous drugs are being compounded, a Class II BSC or III BSC or an isolator intended for aseptic preparation and containment is required.

 A Class II BSC has an open front with inward airflow for personnel protection,downward HEPA-filtered laminar airflow for product protection, and HEPA-filtered exhausted air for environmental protection,a common exhaust plenum, may exhaust HEPA- filtered air back into the laboratory or to the environment through an exhaust canopy.  Effectiveness of such cabinets depends on operators’ use of proper technique.

 Isolator may be considered a ventilated controlled environment that has fixed walls, floor, and ceiling.  For sterile preparations: ISO class 5 for filtered air and airflow as a way to minimize the challenges of a traditional cleanroom and some of the disadvantages of the Class II BSC.  The totally enclosed design may reduce the escape of contamination during the compounding process. The isolator may be less sensitive to drafts and other laminar- airflow equipment, including positive-pressure environments (a fixed-glove assembly).

Horizontal Laminar Flow Clean Bench DO NOT USE FOR HAZARDOUS DRUGS!! Diagram courtesy of Duane Hammon, Ken Mead, Div. of Applied Research and Technology, Engineering and Physical Hazards Branch, CDC.

Environment Keep potentially contaminated PPE away from face, skin NEVER eat or drink in hazardous drug prep area Wear gown properly What NOT to do today….. Photos courtesy of Robert DeChristoforo, MS Deputy Chief, Pharmacy Dept., NIH Clinical Center Pharmacy

Photo courtesy of Luci A. Power, MS Senior Pharmacist, Manager, UCSF-IV Additive Service

Photo courtesy of Luci A. Power, MS Senior Pharmacist, Manager, UCSF-IV Additive Service

Class III BSC Similar to isolator with gloveports Similar to isolator with gloveports Totally enclosed, ventilated, leak-tight, negative air pressure Totally enclosed, ventilated, leak-tight, negative air pressure Operations through attached gloves Operations through attached gloves Highly toxic or infectious materials Highly toxic or infectious materials Seldom used for sterile products compounding Seldom used for sterile products compounding Diagram courtesy of Duane Hammon, Ken Mead, Div. of Applied Research and Technology, Engineering and Physical Hazards Branch, CDC.

5- Rooms and Equipment (ct’d) B) Make ready room Materials needed for the preparation Materials needed for the preparation Solutions ready for dispatch Solutions ready for dispatch C) Air Lock One room One room Two separate rooms Two separate rooms Windows integrated in the door Windows integrated in the door Sliding mechanism to open the window to the preparation room Sliding mechanism to open the window to the preparation room

5- Rooms and Equipment (ct’d) 5- Rooms and Equipment (ct’d) D) Preparation room (1) Room size : min 10 m² Room size : min 10 m² Height : min 2.50m Height : min 2.50m Walls, ceilings and floors Walls, ceilings and floors Cleanness of the room Cleanness of the room E) Preparation room (2) Safety workbench Safety workbench Two way intercom Two way intercom Storage facilities for limited quantities of drugs Storage facilities for limited quantities of drugs Cleaned seatings Cleaned seatings Waste containers Waste containers Decontamination kit Decontamination kit Possibility of direct documentation of the preparation Possibility of direct documentation of the preparation

1. The use of a Class II or III BSC or isolator must be accompanied by a stringent program of work practices, including operator training for contamination reduction, and decontamination. 2. Do not place unnecessary items in the work area of the cabinet or isolator where hazardous drug contamination from compounding may settle on them. 3. Do not overcrowd the BSC or isolator. 4. Gather all needed supplies before beginning compounding. Avoid exiting and reentering the work area of the BSC or isolator.

5. Appropriate handling of the preparation in the BSC or pass-through of the isolator, including spraying or wiping with 70% alcohol or another appropriate disinfectant, is necessary for aseptic compounding (The work surface of the safety cabinet should be covered with plastic-backed absorbent paper. This will reduce the potential for dispersion of droplets and spills and facilitate cleanup). 6. Reduce the hazardous drug contamination burden in the BSC or isolator by wiping down hazardous drug vials before placing them in the BSC or isolator. 7. Transport bags must never be placed in the BSC or the isolator work chamber during compounding to avoid inadvertent contamination of the outside surface of the bag.

8. Final preparations should be surface decontaminated within the BSC or isolator and placed into the transport bags in the BSC or in the isolator pass-through, taking care not to contaminate the outside of the transport bag. 9. Decontaminate the work surface of the BSC or isolator before and after compounding per the manufacturer’s recommendations or with detergent, sodium hypochlorite solution, and neutralizer. 10. Decontaminate all surfaces of the BSC or isolator at the end of the batch, day, or shift, as appropriate to the workflow. Typically, a BSC or isolator in use 24 hours a day would require decontamination two or three times daily. Disinfect the BSC or isolator before compounding a dose or batch of sterile hazardous drugs.

11. Wipe down the outside of the Class II BSC front opening and the floor in front of the BSC with detergent, sodium hypochlorite solution, and neutralizer at least daily. 12. Seal and then decontaminate surfaces of waste and sharps containers before removing from the BSC or isolator. 13. Decontamination is required after any spill in the BSC or isolator during compounding. 14. Seal all contaminated materials (e.g., gauze, wipes, towels, wash or rinse water) in bags or plastic containers and discard as contaminated waste.

16. Appropriate decontamination within the cabinet must be completed before the cabinet is accessed via the pass- throughs or removable front panels. 17. Gloves or gauntlets must not be replaced before completion of appropriate decontamination within the cabinet. 18. Surface decontamination of final preparations must be done before labeling and placing into the passthrough. 19. Final preparations must be placed into a transport bag while in the pass-through for removal from the cabinet.

Surface Inactivation Surface Safe® Surface Safe® Two-step inactivator system Two-step inactivator system First pad: 7 mL of 2% w/v sodium hypochlorite in 0.2% 2/v dodecylsulfate First pad: 7 mL of 2% w/v sodium hypochlorite in 0.2% 2/v dodecylsulfate Second pad: 9 mL of 1% w/v sodium thiosulfate to inactivate and remove bleach Second pad: 9 mL of 1% w/v sodium thiosulfate to inactivate and remove bleach Chemical reaction results in formation of table salt, water, and inorganic sulfides Chemical reaction results in formation of table salt, water, and inorganic sulfides Step 3: Water or isopropyl alcohol to remove residue Step 3: Water or isopropyl alcohol to remove residue Apply at least once per shift for low volume; two to three times per shift for high volume Apply at least once per shift for low volume; two to three times per shift for high volume Apply immediately after known minor spill or leak Apply immediately after known minor spill or leak Reference: Contemporary Issues in the Safe Handling of Cytotoxic Agents: Exhibitors’ Theater, December 4 th, 2001, ASHP Midyear Clinical Meeting

It is the third measure to be taken in addition to organizational measures and the technical equipment

6- Personal Protective Equipment Appropriate Personal Protective Equipment (PPE) Gloves Gowns Eye Protection –When splashing is possible Respirator/masks –For aerosols & spill clean-up Shoe & Hair covering Source: Safe handling of cytotoxic drugs: an independent study module. 2nd ed. Pittsburgh (PA): Oncology Nursing Society; p26 19

ASHP Guidelines: Appendix C Recommendations for Use of Gloves Double gloves for all activities involving hazardous drugs Double gloves for all activities involving hazardous drugs Powder-free, latex, nitrile, polyurethane, neoprene, other materials meeting ASTM standard for chemotherapy gloves Powder-free, latex, nitrile, polyurethane, neoprene, other materials meeting ASTM standard for chemotherapy gloves Inspect for visible defects Inspect for visible defects Sanitize with 70% alcohol or other disinfectant Sanitize with 70% alcohol or other disinfectant CHANGE GLOVES EVERY 30 MINUTES or immediately when damaged or contaminated CHANGE GLOVES EVERY 30 MINUTES or immediately when damaged or contaminated

ASHP Guidelines: Appendix C Recommendations for Use of Gloves Remove outer gloves after wiping down final prep but before labeling or removing from BSC Remove outer gloves after wiping down final prep but before labeling or removing from BSC Place outer gloves in a containment bag within the BSC Place outer gloves in a containment bag within the BSC Wear a second glove inside the fixed glove within an isolator Wear a second glove inside the fixed glove within an isolator Clean fixed gloves after compounding is complete Clean fixed gloves after compounding is complete Wash hands before gloving and after removing gloves Wash hands before gloving and after removing gloves

Photo courtesy of Luci A. Power, MS Senior Pharmacist, Manager, UCSF-IV Additive Service

Photo courtesy of Luci A. Power, MS Senior Pharmacist, Manager, UCSF-IV Additive Service

Personal Protective Equipment

Training on Handling of Hazardous Medications Appropriate Personal Protective Equipment (PPE) - continued Gowns –Wear gowns that are disposable, made of a lint-free, low- permeability fabric. –They should have a solid front (back closure) and knit or elastic cuffs. –Laboratory coats and other cloth fabrics absorb fluids, so they provide an inadequate barrier to hazardous drugs and are not recommended. Source: Safe handling of cytotoxic drugs: an independent study module. 2nd ed. Pittsburgh (PA): Oncology Nursing Society; p26 25

ASHP Guidelines: Appendix D Recommendations for Use of Gowns Should be worn during compounding, administration, handling waste from patients recently treated with hazardous drugs, and cleaning up (small) spills of hazardous drugs Should be worn during compounding, administration, handling waste from patients recently treated with hazardous drugs, and cleaning up (small) spills of hazardous drugs Coated gowns (polyethylene or vinyl coatings) may be worn up to 3 hours. Uncoated polypropylene and polypropylene-polyethylene copolymer provide little protection. Coated gowns (polyethylene or vinyl coatings) may be worn up to 3 hours. Uncoated polypropylene and polypropylene-polyethylene copolymer provide little protection.

ASHP Guidelines: Appendix D Recommendations for Use of Gowns Gowns should be disposed immediately as contaminated waste upon removal and not hung up for later use in the pharmacy compounding area. Gowns should be disposed immediately as contaminated waste upon removal and not hung up for later use in the pharmacy compounding area. Gowns are still prudent when using an isolator or Class III BSC due to possible exposure outside the cabinet. Gowns are still prudent when using an isolator or Class III BSC due to possible exposure outside the cabinet. Wash hands after removing and disposing of gowns. Wash hands after removing and disposing of gowns.

7- Technical Equipment 3-layer work underlay Sterile compresses and swabs Single-use syringes Cannulas (needles) Container for discarded cannulas Waste container Closed system, Drug-transfer devices (Mixing adaptor, phaseal,…)

8- Manipulative Procedures General Techniques (Use of luer-lock syringes….) Aseptic & Negative pressure Techniques Validation: Rooms with respect of cleaning and hygiene Cytostatics workbench Work materials Starting materials Aseptic Technique: Demonstration of Competence

What is a Closed-System? “A closed system drug transfer device mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system” NIOSH* * National Institute for Occupational Safety & Health 34