(10) “ISO Class 7” means conditions in which the air particle count is no greater than a total of 352,000 particles of 0.5 micrometers and larger per cubic meter of air that is supplied by HEPA or HEPA-filtered air.
(11) “ISO Class 8” means conditions in which the air particle count is no greater than a total of 3,520,000 particles of 0.5 micrometers and larger per cubic meter of air that is supplied by HEPA or HEPA-filtered air.
(12) “Isolator” means an enclosure that provides HEPA-filtered ISO Class 5 unidirectional air operated at a continuously higher pressure than its surrounding environment and is decontaminated using an automated system. An isolator uses only decontaminated interfaces or rapid transfer ports for materials transfer.
(13) “Primary engineering control” means a device or zone that provides an ISO Class 5 environment for sterile compounding.
(14) “Restricted access barrier system (RABS)” means an enclosure that provides HEPA filtered ISO Class 5 unidirectional air that allows for the ingress or egress of materials through defined openings that have been designed and validated to preclude the transfer of contamination, and that generally are not to be opened during operations. RABS include compounding aseptic isolators and compounding aseptic containment isolators.
(15) “Sterility assurance level of 10-6” means an equivalent to a probability that 1 unit in a million is nonsterile.
(16) “Segregated compounding area” means a designated, unclassified space, area, or room that contains a primary engineering control.
(17) “Urgent use compounded sterile preparation” means a preparation needed urgently for a single patient and preparation of the compounded sterile preparation under Category 1 or Category 2 requirements would subject the patient to additional risk due to delays.
15.31 Facility design and environmental controls. (1) General. Facilities shall meet all of the following requirements:
(a) Be physically designed and environmentally controlled to minimize airborne contamination from contacting critical sites.
(b) Be accessible only to designated personnel.
(c) Have a heating, ventilation, and air conditioning system controlling the temperature and humidity.
(2) Segregated compounding area. A segregated compounding area shall meet all of the following requirements:
(a) Be located in an area away from unsealed windows and doors that connect to the outdoors, or significant traffic flow.
(b) Be located in an area which is not adjacent to construction sites, warehouses and food preparation areas.
(c) Have a defined perimeter.
(d) Locate the primary engineering control at least 1 meter from any sink.
(3) Classified area. A classified area shall meet all of the following:
(a) The surfaces of ceilings, walls, floors, fixtures, shelving, counters and cabinets shall be smooth, impervious, free from cracks and crevices and nonshedding.
(b) Work surfaces shall be constructed of smooth, impervious materials. All work surfaces shall be resistant to damage from cleaning and sanitizing agents.
(c) Junctures where ceilings meet walls shall be covered, caulked, or sealed to avoid cracks and crevices in which microorganisms and other contaminate can accumulate. All areas in ceilings and walls where the surface has been penetrated shall be sealed.
(d) Ceilings that consist of inlaid panels shall be impregnated with a polymer to render them impervious and hydrophobic and shall either be caulked or weighted and clipped.
(e) Walls shall be constructed of a durable material, panels locked together and sealed or of epoxy-coated gypsum board.
(f) Floors shall have a covering that shall be seamless or have heat-welded seams and coving to the sidewall. There shall be no floor drains.
(g) All sprinkler heads shall be flush with the ceiling.
(h) Ceiling lighting fixtures shall have exterior lens surfaces which are smooth, mounted flush and sealed.
(i) Carts shall be constructed of stainless steel wire, nonporous plastic or sheet metal with cleanable casters.
(j) Tacky mats may not be used in a classified area.
(k) HEPA filters and unidirectional airflow shall be used to maintain the appropriate airborne particulate classification.
(L) The classified area shall measure not less than 30 air changes per hour of which at least half shall be HEPA-filtered fresh air.
(m) A minimum differential positive pressure of 0.02-inch water column is required to separate each classified area. A pressure gauge or velocity meter shall be used to monitor the pressure differential or airflow between classified areas with results documented at least daily.
(n) Devices and objects essential to compounding shall be located at an appropriate distance from the primary engineering control.
(o) The ante area and buffer area shall be separate rooms, with walls and doors between them and controls to prevent the flow of lower quality air into the higher ISO class areas. If a pass through is used, only one door shall be opened at a time.
(p) The ante area shall meet all of the following requirements:
1. Be capable of maintaining an ISO class 8 air or higher.
2. Have a sink with running hot and cold running water.
(q) The buffer area shall meet all of the following requirements:
1. Be capable of maintaining an ISO class 7 air or better.
2. Only contain any of the following:
a. Items, including furniture, equipment, and supplies, that are required for the tasks to be performed in the buffer area.
b. Items that are smooth, impervious, free from cracks and crevices, nonshedding, and easily cleaned and disinfected.
c. Items that have been cleaned and disinfected immediately prior to their being placed in the buffer area.
3. Does not contain any sinks.
4. Does not contain any course cardboard, external shipping containers and nonessential paper.
(4) Primary engineering control. The primary engineering control shall be certified by an independent, qualified individual prior to initial use and then every six months. It shall also be certified when any of the following occurs:
(a) Redesign of the facility.
(b) Replacement of the primary engineering control.
(c) Relocation of the primary engineering control.
15.32 Personnel hygiene, garbing and protective gear. (1) Personnel suffering from rashes, sunburn, oozing tattoos or sores, conjunctivitis, active respiratory infection, or other active communicable disease shall be excluded from working in compounding areas until the condition is resolved.
(2) All personnel who engage in compounding sterile preparations shall comply with all of the following requirements before entering the compounding area:
(a) Remove personal outer garments, all cosmetics, exposed jewelry and piercings, headphones, ear buds, and cell phones.
(b) Abstain from eating, chewing gum or drinking in the compounding area or bringing food, gum or drink into the compounding area.
(c) Artificial nails, nail extenders or nail polish may not be worn while working in the compounding area. Nails shall be neat and trim.
(d) Personnel protective equipment shall be put on in the following order:
1. Low-lint, disposable shoe covers.
2. Low-lint, disposable covers for head and facial hair that cover the ears and forehead.
3. Face masks if compounding Category 2 compounded sterile preparations using laminar airflow system and biological safety cabinet.
4. Eye shields, if required due to working with irritants or hazardous drugs.
(e) A hand hygiene procedure shall be performed after performing the protective equipment in par (d). The hand hygiene procedure includes all of the following:
1. Wash hands and forearms up to the elbows with unscented soap and water for at least 30 seconds.
2. Hands and forearms to the elbows shall be completely dried using either lint-free disposable towels or wipes.
3. Prior to donning sterile gloves hand antisepsis shall be performed using an alcohol-based hand rub with sustained antimicrobial activity following the manufacturers labeled instructions and application times.
(f) Personnel shall wear one of the following:
1. Non-cotton, low-lint sterile gown and sterile gloves.
2. Non-cotton, low-lint gown, sterile sleeves and sterile gloves.
(3) Gloves on hands and gauntlet sleeves on RABS shall be routinely inspected for holes, punctures, or tears and shall be replaced immediately if any are detected.
(4) Disinfection of contaminated gloved hands shall be accomplished by wiping or rubbing sterile 70% isopropyl alcohol on all contact surface areas of the gloves and letting the gloved hands dry thoroughly. Routine application of sterile 70% isopropyl alcohol shall occur throughout the compounding process and whenever non-sterile surfaces, including vials, counter tops, chairs and carts, are touched.
(5) When compounding personnel exit the buffer or segregated compounding area during a work shift, a nonsterile gown may be removed and retained in the ante area or segregated compounding area if not visibly soiled, to be worn again during the same work shift. Coveralls, sterile gowns, shoe covers, hair and facial hair covers, face masks, eye shields, gloves and sleeves shall be replaced with new ones before re-entering the compounding area.
(6) Garbing items, including gowns, shall be segregated and stored before use in an enclosure to prevent contamination.
(7) Coveralls and sterile gowns shall not be reused. Visibly soiled gowns shall be changed immediately.
(8) Gloves shall be sterile and powder free and tested by the manufacturer for compatibility with alcohol disinfection.
15.33 Cleaning and Disinfecting the Compounding Area. (1) Compounding personnel are responsible determining the cleaning and disinfecting products to be used and for ensuring that the frequency of cleaning and disinfecting compounding area is done in accordance with the following minimum frequency:
(a) Primary engineering control work surfaces, excluding isolators, at the beginning of each shift, end of each shift and before each batch, but not longer than 30 minutes following the previous surface disinfection when ongoing compounding activities are occurring.
(b) Counters and work surfaces outside the primary engineering control in the buffer area, ante room and segregated compounding areas daily.
(c) Floors daily.
(d) Walls, ceilings and storage shelving monthly.
(2) An isolator shall be cleaned each time it is opened and decontaminated once it is closed after each time it is opened. If cleaning occurs without opening, decontaminate after each cleaning cycle.
(3) Cleaning and disinfecting sterile compounding areas shall occur on a regular basis at the intervals in sub. (1) or when any of the following occurs:
(a) Spills occur.
(b) The surface is visibly soiled.
(c) Microbial contamination is known to have been or is suspected of having been introduced into the compounding area.
(4) All cleaning and disinfecting practices and policies for the compounding area shall be included in written standard operating procedures and shall be followed by all compounding and environmental services personnel.
(5) Cleaning, detergents and disinfection agents shall be selected and used with consideration of compatibilities, effectiveness and inappropriate or toxic residues. The selection and use of disinfectants shall be guided by microbicidal activities, inactivation by organic matter, residue, and shelf life. Disinfectants shall have antifungal, antibacterial and antiviral activity. Sporicidal agents shall be used at least weekly to clean compounding areas.
(6) Storage sites for compounding ingredients and supplies shall remain free from dust and debris.
(7) Floors, walls, ceiling and shelving in the classified and segregated compounding areas are cleaned when no aseptic operations are in progress. Cleaning shall be performed in the direction from cleanest to dirtiest areas.
(8) All cleaning tools and materials shall be sterile, low-lint and dedicated for use in the buffer room, ante room and segregated compounding areas. If cleaning tools and materials are reused, procedures shall be developed based on manufacturer recommendations that ensure that the effectiveness of the cleaning device is maintained and that repeated use does not add to the bioburden of the area being cleaned.
