Chapter Phar 15

Phar 15.30(14r) (14r) “Medium-risk level compounded sterile preparations” means preparations compounded under low-risk level conditions but which require multiple individual or small doses of sterile products to be combined or pooled to prepare compounded sterile preparations that will be administered either to multiple patients or to one patient on multiple occasions. The medium-risk level sterile compounding process includes complex aseptic manipulations other than single volume transfer, and requires an unusually long duration, such as that required to complete dissolution or homogeneous mixing.

Phar 15.30(15) (15) “Primary engineering control” means a device or zone that provides an ISO Class 5 environment for sterile compounding.

Phar 15.30(16) (16) “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.

Phar 15.30(17) (17) “Sterility assurance level of 10-6” means an equivalent to a probability that one unit in a million is nonsterile.

Phar 15.30(18) (18) “Segregated compounding area” means a designated, unclassified space, area, or room that contains a primary engineering control.

Phar 15.30(19) (19) “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.

Phar 15.30 History History: CR 16-085: cr. Register April 2018 No. 748 eff. 11-1-18; CR 22-007: cr. (10m), (14g), (14r) Register July 2022 No. 799, eff. 8-1-22.

Phar 15.31 Phar 15.31 Facility design and environmental controls.

Phar 15.31(1) (1) General. Facilities shall meet all of the following requirements:

Phar 15.31(1)(a) (a) Be physically designed and environmentally controlled to minimize airborne contamination from contacting critical sites.

Phar 15.31(1)(b) (b) Be accessible only to designated personnel.

Phar 15.31(1)(c) (c) Have a heating, ventilation, and air conditioning system controlling the temperature and humidity.

Phar 15.31(2) (2) Segregated compounding area. A segregated compounding area shall meet all of the following requirements:

Phar 15.31(2)(a) (a) Be located in an area away from unsealed windows and doors that connect to the outdoors, or significant traffic flow.

Phar 15.31(2)(b) (b) Be located in an area which is not adjacent to construction sites, warehouses, and food preparation areas.

Phar 15.31(2)(c) (c) Have a defined perimeter.

Phar 15.31(2)(d) (d) Locate the primary engineering control at least one meter from any sink.

Phar 15.31(3) (3) Classified area. A classified area shall meet all of the following:

Phar 15.31(3)(a) (a) The surfaces of ceilings, walls, floors, fixtures, shelving, counters, and cabinets shall be smooth, impervious, free from cracks and crevices, and nonshedding.

Phar 15.31(3)(b) (b) Work surfaces shall be constructed of smooth, impervious materials. All work surfaces shall be resistant to damage from cleaning and sanitizing agents.

Phar 15.31(3)(c) (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.

Phar 15.31(3)(d) (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.

Phar 15.31(3)(e) (e) Walls shall be constructed of a durable material, panels locked together and sealed or of epoxy-coated gypsum board.

Phar 15.31(3)(f) (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.

Phar 15.31(3)(h) (h) Ceiling lighting fixtures shall have exterior lens surfaces which are smooth, mounted flush, and sealed.

Phar 15.31(3)(i) (i) Carts shall be constructed of stainless steel wire, nonporous plastic or sheet metal with cleanable casters.

Phar 15.31(3)(j) (j) Tacky mats may not be used in a classified area.

Phar 15.31(3)(k) (k) HEPA filters and unidirectional airflow shall be used to maintain the appropriate airborne particulate classification.

Phar 15.31(3)(L) (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.

Phar 15.31(3)(m) (m) For classified areas physically separated through the use of walls, doors, and pass-throughs, a minimum differential positive pressure of 0.02-inch water column is required to separate each classified area. If a pass-through is used, only one door shall be opened at a time. 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.

Phar 15.31(3)(mm) (mm) For classified areas not physically separated, no sterile compounded preparation may be compounded using any ingredient that was at any time non-sterile in a classified area not physically separated and all of the following shall be met:

Phar 15.31(3)(mm)1. 1. The buffer and ante areas shall be designated with a line of demarcation.

Phar 15.31(3)(mm)2. 2. The principle of displacement airflow shall be used with an air velocity of 40 feet per minute or more from the buffer area across the entire plane of the line of demarcation.

Phar 15.31(3)(n) (n) Devices and objects essential to compounding shall be located at an appropriate distance from the primary engineering control.

Phar 15.31(3)(p) (p) The ante area shall meet all of the following requirements:

Phar 15.31(3)(p)1. 1. Be capable of maintaining an ISO Class 8 air or higher.

Phar 15.31(3)(p)2. 2. Have a sink with running hot and cold running water.

Phar 15.31(3)(q) (q) The buffer area shall meet all of the following requirements:

Phar 15.31(3)(q)1. 1. Be capable of maintaining an ISO Class 7 air or better.

Phar 15.31(3)(q)2. 2. Only contain any of the following:

Phar 15.31(3)(q)2.a. a. Items, including furniture, equipment, and supplies, that are required for the tasks to be performed in the buffer area.

Phar 15.31(3)(q)2.b. b. Items that are smooth, impervious, free from cracks and crevices, nonshedding, and easily cleaned and disinfected.

Phar 15.31(3)(q)2.c. c. Items that have been cleaned and disinfected immediately prior to their being placed in the buffer area.

Phar 15.31(3)(q)3. 3. Does not contain any sinks.

Phar 15.31(3)(q)4. 4. Does not contain any course cardboard, external shipping containers, and nonessential paper.

Phar 15.31(4) (4) Primary engineering control. The primary engineering control shall be certified by an independent, qualified individual certified by the Controlled Environment Testing Association’s National Board of Testing or another Board approved entity prior to initial use and then every six months. It shall also be certified when any of the following occurs:

Phar 15.31(4)(a) (a) Redesign of the facility.

Phar 15.31(4)(b) (b) Replacement of the primary engineering control.

Phar 15.31(4)(c) (c) Relocation of the primary engineering control.

Phar 15.31 History History: CR 16-085: cr. Register April 2018 No. 748 eff. 11-1-18.

Phar 15.32 Phar 15.32 Personnel hygiene, garbing and protective gear.

Phar 15.32(1) (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.

Phar 15.32(2) (2) All personnel who engage in compounding sterile preparations shall comply with all of the following requirements before entering the compounding area:

Phar 15.32(2)(a) (a) Remove personal outer garments, all cosmetics, exposed jewelry and piercings, headphones, ear buds, and cell phones.

Phar 15.32(2)(b) (b) Abstain from eating, chewing gum or drinking in the compounding area or bringing food, gum, or drink into the compounding area.

Phar 15.32(2)(c) (c) Artificial nails, nail extenders or nail polish may not be worn while working in the compounding area. Nails shall be neat and trim.

Phar 15.32(2)(d) (d) Don personnel protective equipment and perform hand hygiene in the following order:

Phar 15.32(2)(d)1. 1. Low-lint, disposable shoe covers.

Phar 15.32(2)(d)2. 2. Low-lint, disposable covers for head and facial hair that cover the ears and forehead and face masks.

Phar 15.32(2)(d)3. 3. Eye shields, if required due to working with irritants or hazardous drugs.

Phar 15.32(2)(d)4. 4. Wash hands and forearms up to the elbows with unscented soap and water for at least 30 seconds. Hands and forearms to the elbows shall be completely dried using either lint-free disposable towels or wipes.

Phar 15.32(2)(d)5. 5. Don low lint disposable gown or overalls.

Phar 15.32(2)(d)6. 6. 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.

Phar 15.32(3) (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. Sterile gloves shall be donned over the RABS gloves.

Phar 15.32(4) (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.

Phar 15.32(5) (5) When compounding personnel exit the buffer or segregated compounding area, a 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, shoe covers, hair and facial hair covers, face masks, eye shields, and gloves shall be replaced with new ones before re-entering the compounding area.

Phar 15.32(6) (6) Garbing items, including gowns, shall be segregated and stored before use in an enclosure to prevent contamination.

Phar 15.32(7) (7) Visibly soiled gowns shall be changed immediately.

Phar 15.32(8) (8) Gloves shall be sterile and powder free and tested by the manufacturer for compatibility with alcohol disinfection.

Phar 15.32 History History: CR 16-085: cr. Register April 2018 No. 748 eff. 11-1-18.

Phar 15.33 Phar 15.33 Cleaning and Disinfecting the Compounding Area and Supplies.

Phar 15.33(1) (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.

Phar 15.33(2) (2) Compounding personnel shall clean in accordance with the following:

Phar 15.33(2)(a) (a) Primary engineering control work surfaces, counters, floors and work surfaces in the buffer zone area, ante room and segregated compounding areas daily.

Phar 15.33(2)(b) (b) Walls, ceilings and storage shelving monthly.

Phar 15.33(2)(c) (c) When a spill occurs or the surface is visibly soiled.

Phar 15.33(2)(d) (d) Sporicidal agents shall be used at least weekly to clean compounding areas.

Phar 15.33(3) (3) Compounding personnel shall disinfect in accordance with the following:

Phar 15.33(3)(a) (a) Primary engineering control work surfaces at the beginning and end of each compounding business day and before each batch, but not longer than 4 hours following the previous disinfection when ongoing compounding activities are occurring.

Phar 15.33(3)(b) (b) When microbial contamination is known to have been or is suspected of having been introduced into the compounding area.

Phar 15.33(4) (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.

Phar 15.33(5) (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.

Phar 15.33(6) (6) Storage sites for compounding ingredients and supplies shall remain free from dust and debris.

Phar 15.33(7) (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.

Phar 15.33(8) (8) All cleaning tools and materials shall be 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.

Phar 15.33(9) (9) Supplies and equipment removed from shipping cartons shall be wiped with a suitable disinfecting agent delivered from a spray bottle or other suitable delivery method. After the disinfectant is wiped on a surface to be disinfected, the disinfectant shall be allowed to dry, during which time the item shall not be used for compounding purposes.

Phar 15.33(10) (10) Entry points on bags and vials shall be wiped with small sterile 70% isopropyl alcohol swabs or comparable method for disinfecting, allowing the isopropyl alcohol to dry before piercing stoppers with sterile needles and breaking necks of ampules. The surface of the sterile 70% isopropyl alcohol swabs used for disinfecting entry points of sterile package and devices may not contact any other object before contacting the surface of the entry point. Particle generating material may not be used to disinfect the sterile entry points of packages and devices.

Phar 15.33(11) (11) When sterile supplies are received in sealed pouches designed to keep them sterile until opening, the sterile supplies may be removed from the covering pouches as the supplies are introduced into the ISO Class 5 primary engineering control without the need to disinfect the individual sterile supply items.

Phar 15.33 History History: CR 16-085: cr. Register April 2018 No. 748 eff. 11-1-18; CR 22-007: am. (10) Register July 2022 No. 799, eff. 8-1-22.