Section 1735.1 - Compounding Definitions(a) "Ante-area" means an area with ISO Class 8 or better air quality where personnel hand hygiene and garbing procedures, staging of components, and other high-particulate-generating activities are performed, that is adjacent to the area designated for sterile compounding. It is a transition area that begins the systematic reduction of particles, prevents large fluctuations in air temperature and pressures in the cleanroom, and maintains air flows from clean to dirty areas. ISO Class 7 or better air quality is required for ante-areas providing air to a negative pressure room.(b) "Beyond use date" means the date, or date and time, after which administration of a compounded drug preparation shall not begin, the preparation shall not be dispensed, and the preparation shall not be stored (other than for quarantine purposes).(c) "Biological Safety Cabinet (BSC)" means a ventilated cabinet for compounding sterile drug preparations, having 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. Where hazardous drugs are prepared, the exhaust air from the biological safety cabinet shall be appropriately removed by properly designed external building exhaust. This external exhaust should be dedicated to one BSC or CACI.(d) "Bulk drug substance" means any substance that, when used in the preparation of a compounded drug preparation, processing, or packaging of a drug, is an active ingredient or a finished dosage form of the drug, but the term does not include any intermediate used in the synthesis of such substances.(e) "Cleanroom or clean area or buffer area" means a room or area with HEPA-filtered air that provides ISO Class 7 or better air quality where the primary engineering control (PEC) is physically located. (1) For nonhazardous compounding a positive pressure differential of 0.02- to 0.05-inch water column relative to all adjacent spaces is required.(2) For hazardous compounding at least 30 air changes per hour of HEPA-filtered supply air and a negative pressure of between 0.01 to 0.03 inches of water column relative to all adjacent spaces is required.(f) "Compounding Aseptic Containment Isolator (CACI)" means a unidirectional HEPA-filtered airflow compounding aseptic isolator (CAI) designed to provide worker protection from exposure to undesirable levels of airborne drug throughout the compounding and material transfer processes and to provide an aseptic environment for compounding sterile preparations. Air exchange with the surrounding environment should not occur unless the air is first passed through a microbial retentive filter (HEPA minimum) system capable of containing airborne concentrations of the physical size and state of the drug being compounded. Where hazardous drugs are prepared, the exhaust air from the isolator shall be appropriately removed by properly designed external building exhaust. This external exhaust should be dedicated to one BSC or CACI. Air within the CACI shall not be recirculated nor turbulent.(g) "Compounding Aseptic Isolator (CAI)" means a form of isolator specifically designed for non-hazardous compounding of pharmaceutical ingredients or preparations while bathed with unidirectional HEPA-filtered air. It is designed to maintain an aseptic compounding environment within the isolator throughout the compounding and material transfer processes. Air exchange into the isolator from the surrounding environment should not occur unless the air has first passed through a microbial retentive filter (HEPA minimum) system capable of containing airborne concentrations of the physical size and state of the drug being compounded. Air within the CAI shall not be recirculated nor turbulent.(h) "Controlled cold temperature" means 2 degrees to 8 degrees C (35 degrees to 46 degrees F).(i) "Controlled freezer temperature" means -25 degrees to -10 degrees C (-13 degrees to 14 degrees F) or at a range otherwise specified by the pharmaceutical manufacturer(s) for that product.(j) "Controlled room temperature" means 20 degrees to 25 degrees C (68 degrees to 77 degrees F).(k) "Copy or essentially a copy" of a commercially available drug product includes all preparations that are comparable in active ingredients to commercially available drug products, except that it does not include any preparations in which there has been a change, made for an identified individual patient, which produces for that patient a clinically significant difference, as determined by a prescribing practitioner, between that compounded preparation and the comparable commercially available drug product.(l) "Daily" means occurring every day the pharmacy is operating, except when daily monitoring of refrigerator and freezer temperature are required, then daily means every 24 hours.(m) "Displacement airflow method" means a concept which utilizes a low pressure differential, high airflow principle to maintain segregation from the adjacent ante-area by means of specific pressure differentials. This principle of displacement airflow shall require an air velocity of 40 ft per minute or more, from floor to ceiling and wall to wall, from the clean area across the line of demarcation into the ante-area. The displacement concept may not be used to maintain clean area requirements for sterile compounds which originate from any ingredient that was at any time non-sterile, regardless of intervening sterilization of the ingredient, or for hazardous compounds.(n) "Dosage unit" means a quantity sufficient for one administration to one patient.(o) "Equipment" means items that must be calibrated, maintained or periodically certified.(p) "First air" means the air exiting the HEPA filter in a unidirectional air stream that is essentially particle free.(q) "Gloved fingertip sampling" means a process whereby compounding personnel lightly press each fingertip and thumb of each hand onto appropriate growth media, which are then incubated at a temperature and for a time period conducive to multiplication of microorganisms, and then examined for growth of microorganisms.(r) "Hazardous" means all anti-neoplastic agents identified by the National Institute for Occupational Safety and Health (NIOSH) as meeting the criteria for a hazardous drug and any other drugs, compounds, or materials identified as hazardous by the pharmacist-in-charge.(s) "Integrity" means retention of potency until the beyond use date provided on the label, so long as the preparation is stored and handled according to the label directions.(t) "Lot" means one or more compounded drug preparation(s) prepared during one uninterrupted continuous cycle of compounding from one or more common active ingredient(s).(u) "Media-fill test" means a test used to measure the efficacy of compounding personnel in aseptic techniques whereby compounding procedures are mimicked using a growth-based media and then the resulting preparation is evaluated for sterility. The media-fill test must mimic the most complex compounding procedures performed by the pharmacy.(v) "Non-sterile-to-sterile batch" means any compounded drug preparation containing two (2) or more dosage units with any ingredient that was at any time non-sterile, regardless of intervening sterilization of that ingredient.(w) "Parenteral" means a preparation of drugs administered in a manner other than through the digestive tract. It does not include topical, sublingual, rectal or buccal routes of administration.(x) "Personal protective equipment" means clothing or devices that protect the employee from exposure to compounding ingredients and/or potential toxins and minimize the contamination of compounded preparations. These include shoe covers, head and facial hair covers, face masks, gowns, and gloves.(y) "Potency" means active ingredient strength within +/- 10% (or the range specified in USP37-NF32, 37th Revision, Through 2nd Supplement Effective December 1, 2014) of the labeled amount. Sterile injectable products compounded solely from commercially manufactured sterile pharmaceutical products in a health care facility licensed under section 1250 of the Health and Safety Code are exempt from this definition. For those exempt, the range shall be calculated and defined in the master formula.(z) "Preparation" means a drug or nutrient compounded in a licensed pharmacy; the preparation may or may not be sterile.(aa) "Prescriber's office" or "prescriber office" means an office or suite of offices in which a prescriber regularly sees patients for outpatient diagnosis and treatment. This definition does not include any hospital, pharmacy, or other facility, whether or not separately licensed, that may be affiliated with, adjacent to, or co-owned by, the prescriber's practice environment.(ab) "Primary Engineering Control (PEC)" means a device that provides an ISO Class 5 or better environment through the use of non-turbulent, unidirectional HEPA-filtered first air for compounding sterile preparations. Examples of PEC devices include, but are not limited to, laminar airflow workbenches, biological safety cabinets, sterile compounding automated robots, compounding aseptic isolators, and compounding aseptic containment isolators.(ac) "Process validation" means demonstrating that when a process is repeated within specified limits, the process will consistently produce preparations complying with predetermined requirements. If any aspect of the process is changed, the process would need to be revalidated.(ad) "Product" means a commercially manufactured drug or nutrient evaluated for safety and efficacy by the FDA.(ae) "Quality" means the absence of harmful levels of contaminants, including filth, putrid, or decomposed substances, the absence of active ingredients other than those listed on the label, and the absence of inactive ingredients other than those listed on the master formula document.(af) "Segregated sterile compounding area" means a designated space for sterile-to-sterile compounding where a PEC is located within either a demarcated area (at least three foot perimeter) or in a separate room. Such area or room shall not contain and shall be void of activities and materials that are extraneous to sterile compounding. The segregated sterile compounding area shall not be in a location that has unsealed windows or doors that connect to the outdoors, in a location with high traffic flow, or in a location that is adjacent to construction sites, warehouses, or food preparation. The segregated sterile compounding area shall not have a sink, other than an emergency eye-washing station, located within three feet of a PEC. The segregated sterile compounding area shall be restricted to preparation of sterile-to-sterile compounded preparations. (1) The BUD of a sterile drug preparation made in a segregated sterile compounding area is limited to 12 hours or less as defined by section 1751.8(d).(2) When the PEC in the segregated sterile compounding area is a CAI or a CACI and the documentation provided by the manufacturer shows it meets the requirements listed in section 1751.4(f)(1)-(3), the assigned BUD shall comply with section 1751.8 (a-b) or (d).(ag) "Strength" means amount of active ingredient per unit of a compounded drug preparation.Cal. Code Regs. Tit. 16, § 1735.1
1. New section filed 1-6-2010; operative 7-6-2010 (Register 2010, No. 2).
2. New subsection (a) and subsection relettering filed 2-6-2013; operative 4-1-2013 (Register 2013, No. 6).
3. Amendment filed 9-13-2016; operative 1-1-2017 (Register 2016, No. 38).
4. Amendment of subsections (c) and (f) and amendment of 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.
1. New section filed 1-6-2010; operative 7-6-2010 (Register 2010, No. 2).
2. New subsection (a) and subsection relettering filed 2-6-2013; operative 4-1-2013 (Register 2013, No. 6).
3. Amendment filed 9-13-2016; operative 1/1/2017 (Register 2016, No. 38).
4. Amendment of subsections (c) and (f) and amendment of Note filed 1-30-2019; operative 1/30/2019 pursuant to Government Code section 11343.4(b)(3) (Register 2019, No. 5).