Section 1751.4 - Facility and Equipment Standards for Sterile Compounding(a) No sterile drug preparation shall be compounded if it is known, or reasonably should be known, that the compounding environment fails to meet criteria specified in the pharmacy's written policies and procedures for the safe compounding of sterile drug preparations.(b) During the compounding of sterile drug preparations, access to the areas designated for compounding must be limited to those individuals who are properly attired.(c) All equipment used in the areas designated for compounding must be made of a material that can be easily cleaned and disinfected.(d) Cleaning shall be done using a germicidal detergent and sterile water. The use of a sporicidal agent is required to be used at least monthly. (1) All ISO Class 5 surfaces, work table surfaces, carts, counters, and the cleanroom floor shall be cleaned at least daily. After each cleaning, disinfection using a suitable sterile agent shall occur on all ISO Class 5 surfaces, work table surfaces, carts, and counters.(2) Walls, ceilings, storage shelving, tables, stools, and all other items in the ISO Class 7 or ISO Class 8 environment shall be cleaned at least monthly.(3) Cleaning shall also occur after any unanticipated event that could increase the risk of contamination.(4) All cleaning materials, such as wipers, sponges, and mops, shall be non-shedding and dedicated to use in the cleanroom, or ante-area, and segregated sterile compounding areas and shall not be removed from these areas except for disposal.(e) Disinfection, using a suitable sterile agent, shall also occur on all surfaces in the ISO Class 5 PEC frequently, including: (1) At the beginning of each shift;(2) At least every 30 minutes when compounding involving human staff is occurring or before each lot;(3) After each spill; and(4) When surface contamination is known or suspected.(f) Pharmacies preparing sterile compounded preparations require the use of a PEC that provides ISO Class 5 air or better air quality. Certification and testing of primary and secondary engineering controls shall be performed no less than every six months and whenever the device or area designated for compounding is relocated, altered or a service to the facility is performed that would impact the device or area. Certification must be completed by a qualified technician who is familiar with certification methods and procedures in accordance with CETA Certification Guide for Sterile Compounding Facilities (CAG-003-2006-13, Revised May 20, 2015), which is hereby incorporated by reference. Certification records must be retained for at least 3 years. Unidirectional compounding aseptic isolators or compounding aseptic containment isolators may be used outside of an ISO Class 7 cleanroom if the isolator is certified to meet the following criteria: (1) Particle counts sampled approximately 6-12 inches upstream of the critical exposure site shall maintain ISO Class 5 levels during compounding operations.(2) Not more than 3520 particles (0.5 um and larger) per cubic meter shall be counted during material transfer, with the particle counter probe located as near to the transfer door as possible without obstructing transfer.(3) Recovery time to achieve ISO Class 5 air quality shall be documented and internal procedures developed to ensure that adequate recovery time is allowed after material transfer before and during compounding operations. Compounding aseptic isolators that do not meet the requirements as outlined in this subdivision or are not located within an ISO Class 7 cleanroom may only be used to compound preparations that meet the criteria specified in accordance with subdivision (d) of Section of Title 161751.8 of Title 16, Division 17, of the California Code of Regulations.
(g) Pharmacies preparing sterile hazardous agents shall do so in accordance with Section 505.7.1 of Title 24, Chapter 5, of the California Code of Regulations, requiring a negative pressure PEC. Additionally, each PEC used to compound hazardous agents shall be externally vented. The negative pressure PEC must be certified every six months by a qualified technician who is familiar with CETA Certification Guide for Sterile Compounding Facilities (CAG-003-2006-13, Revised May 20, 2015), which is hereby incorporated by reference. Any drug preparation that is compounded in a PEC where hazardous drugs are prepared must be labeled as hazardous, regardless of whether the drug ingredients are considered hazardous. (1) During the hazardous drug compounding that is performed in a compounding aseptic containment isolator, full hand hygiene and garbing must occur. Garbing shall include hair cover, facemask, beard cover (if applicable), polypropylene or low shedding gown that closes in the back, shoe covers, and two pairs of sterile ASTM D6978-05 standard gloves.(h) If a compounding aseptic isolator is certified by the manufacturer to maintain ISO Class 5 air quality during dynamic operation conditions during compounding as well as during the transfer of ingredients into and out of the compounding aseptic isolator, then it may be placed into a non-ISO classified room. Individuals that use compounding aseptic isolators in this manner must ensure appropriate garbing, which consists of donning sterile gloves over the isolator gloves immediately before non-hazardous compounding. These sterile gloves must be changed by each individual whenever continuous compounding is ceased and before compounding starts again.(i) Compounding aseptic isolator and compounding aseptic containment isolator used in the compounding of sterile drug preparations shall use non-turbulent unidirectional air flow patterns. A smoke patterned test shall be used to determine air flow patterns.(j) Viable surface sampling shall be done at least every six months for all sterile-to-sterile compounding and quarterly for all non-sterile-to-sterile compounding. Viable air sampling shall be done by volumetric air sampling procedures which test a sufficient volume of air (400 to 1,000 liters) at each location and shall be done at least once every six months. Viable surface and viable air sampling shall be performed by a qualified individual who is familiar with the methods and procedures for surface testing and air sampling. Viable air sampling is to be performed under dynamic conditions that simulate actual production. Viable surface sampling is to be performed under dynamic conditions of actual compounding. When the environmental monitoring action levels are exceeded, the pharmacy shall identify the CFUs at least to the genus level in addition to conducting an investigation pursuant to its policies and procedures. Remediation shall include, at minimum, an immediate investigation of cleaning and compounding operations and facility management.(k) The sterile compounding area in the pharmacy shall have a comfortable and well-lighted working environment, which typically includes a room temperature of 20 degrees Celsius (68 degrees Fahrenheit) or cooler to maintain comfortable conditions for compounding personnel when attired in the required compounding garb.(l) A licensee may request a waiver of these provisions as provided in section 1735.6(f).Cal. Code Regs. Tit. 16, § 1751.4
1. New section filed 10-6-86; effective thirtieth day thereafter (Register 86, No. 42).
2. Change without regulatory effect amending NOTE filed 9-11-2002 pursuant to section 100, title 1, California Code of Regulations (Register 2002, No. 37).
3. Amendment of section heading and section filed 9-29-2004; operative 10-29-2004 (Register 2004, No. 40).
4. Renumbering of section 1751.4 to section 1754.5 and renumbering of section 1751.01 to section 1751.4, including amendment of section heading, section and NOTE, filed 1-6-2010; operative 7-6-2010 (Register 2010, No. 2).
5. Amendment of section heading and section filed 9-13-2016; operative 1-1-2017 (Register 2016, No. 38).
6. Change without regulatory effect amending subsection (g) filed 3-20-2017 pursuant to section 100, title 1, California Code of Regulations (Register 2017, No. 12).
7. Amendment of subsection (k) and NOTE filed 1-30-2019; operative 1-30-2019 pursuant to Government Code section 11343.4(b)(3) (Register 2019, No. 5). Note: Authority cited: Sections 4005 and 4127, Business and Professions Code. Reference: Sections 4005, 4029, 4036, 4037, 4051, 4052 and 4127, Business and Professions Code; and Section 18944, Health and Safety Code.
1. New section filed 10-6-86; effective thirtieth day thereafter (Register 86, No. 42).
2. Change without regulatory effect amending Note filed 9-11-2002 pursuant to section 100, title 1, California Code of Regulations (Register 2002, No. 37).
3. Amendment of section heading and section filed 9-29-2004; operative 10-29-2004 (Register 2004, No. 40).
4. Renumbering of section 1751.4 to section 1754.5 and renumbering of section 1751.01 to section 1751.4, including amendment of section heading, section and Note, filed 1-6-2010; operative 7-6-2010 (Register 2010, No. 2).
5. Amendment of section heading and section filed 9-13-2016; operative 1/1/2017 (Register 2016, No. 38).
6. Change without regulatory effect amending subsection (g) filed 3-20-2017 pursuant to section 100, title 1, California Code of Regulations (Register 2017, No. 12).
7. Amendment of subsection (k) and Note filed 1-30-2019; operative 1/30/2019 pursuant to Government Code section 11343.4(b)(3) (Register 2019, No. 5).