Section Ph 404.02 - Definitions(a) "Active pharmaceutical ingredients" means chemicals, substances, or other components of articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases in humans or animals or for use as nutritional supplements.(b) "Added substances" means the ingredients necessary to prepare the drug product but are not intended or expected to cause human pharmacological response if administered alone in the amount or concentration contained in a single doses of the compounded preparation. The term "added substances" includes the terms "inactive ingredients", "excipients", and "pharmaceutical ingredients."(c) "Ante-area" means: (1) An ISO Class 8 or better area where personal perform hand hygiene and garbing procedures, staging of components, order enter, CSP labeling, and other high-particulate-generating activities are performed;(2) A transition area that: a. Provides assurance that pressure relationships are constantly maintained so that air flows from clean to dirty areas; andb. Reduces the need for the heating, ventilating, and air-conditioning (HVAC) control system to respond to large disturbances. (d) "Aseptic processing" means a mode of processing pharmaceutical and medical products that involves the separate sterilization of the product and of the package containers, closures or packaging material for medical devices and the transfer of the product into the container and its closure under at least ISO Class 5 conditions.(e) "Beyond-use date (BUD)" is the date after which a compounded preparation should not to be used; determined from the date the preparation is compounded.(f) "Biological Safety Cabinet (BSC)" means a ventilated cabinet for CSPs, personnel, product, and environmental protection having an open front with inward airflow for personnel protection, downward high-efficiency particulate air (HEPA)-filtered laminar airflow for product protection, and HEPA-filtered exhausted air for environmental protection.(g) "Buffer area" means an area where the primary engineering control (PEC) is physically located.(h) "Clean room" means a room in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. Microorganisms in the environment are monitored so that a microbial level for air, surface, and personnel gear are not exceeded for a specified cleanliness class.(i) "Component" means any ingredient used in the compounding of a drug preparation, including any active ingredient or added substance that is used in its preparation.(j) "Compounder" means a licensed professional authorized by the appropriate jurisdiction to perform compounding pursuant to a prescription or medication order by a licensed prescriber.(k) "Compounding" means the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner's order, or initiative based on the practitioner/patient/pharmacist/compounder relationship in the course of professional practice, and includes the following: (1) Preparation of drug dosage forms for both human and animal patients;(2) Preparation of drugs or devices in anticipation of prescription drug orders based on routine, regularly observed prescribing patterns;(3) Reconstitution or manipulation of commercial products that may require the addition of one or more ingredients;(4) Preparation of drugs or devices for the purposes of, or as an incident to research clinical or academic teaching, or chemical analysis; and(5) Preparation of drugs and devices on the order of a practitioner, which may be sold to the practitioner for use in his or her office to administer to a specific patient, in limited quantities, but not for resale.(l) "Compounding Aseptic Containment Isolator (CACI)" means a 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.(m) "Compounding Aseptic Isolator (CAI)" means a form of isolator specifically designed for compounding pharmaceutical ingredients or preparations. It is designed to maintain an aseptic compounding environment within the isolator throughout the compounding and material transfer processes.(n) "Critical area" means an ISO Class 5 environment.(o) "Critical site" means a location that includes any component or fluid pathway surfaces such as vial septa, injection ports, beakers or openings such as opened ampules or needle hubs exposed and at risk of direct contact with air including ambient room or HEPA filtered, moisture such as oral and mucosal secretions, or touch contamination. Risk of microbial particulate contamination of the critical site increases with the size of the openings and exposure time.(p) "Direct Compounding Area (DCA)" means an area within the ISO Class 5 primary engineering control (PEC) where critical sites are exposed to unidirectional HEPA-filtered air, also known as first air.(q) "Disinfectant" means an agent that frees from infection, usually a chemical agent but sometimes a physical one, and that destroys disease-causing pathogens or other harmful microorganisms but might not kill bacterial and fungal spores. It refers to substances applied to inanimate objects.(r) "First air" means the air exiting the HEPA filter in a unidirectional air stream that is essentially particle free.(s) "Hazardous drugs" means any drug which in studies of animals or humans have been classified as carcinogenic, toxic to development or reproduction, or toxic to organs.(t) "Labeling" means a term that designates all labels and other written, printed, or graphic matter on an immediate container of an article or preparation or on, or in, any package or wrapper in which it is enclosed, except any outer shipping container. The term "label" designates that part of the labeling on the immediate container.(u) "Limited quantities" means a batch with 50 or less dosage units provided to a hospital or practitioner to administer to their own patient.(v) "Manufacturing" means the production, preparation, propagation, conversion or processing of a drug or device, either directly or indirectly, by large volume extraction from substances of natural origin, or independently by means of chemical or biological synthesis, and includes any packaging or repackaging of a substance or labeling or relabeling of its container, and the promotion and marketing of such drugs and devices for resale.(w) "Media-fill test" means a test used to qualify aseptic technique of compounding personnel or processes and to ensure that the processes used are able to produce sterile product without microbial contamination. During this test, a microbiological growth medium such as Soybean-Casein Digest Medium is substituted for the actual drug product to simulate admixture compounding.(x) "Memorandum of understanding" means a document specific to the preparation(s) provided to a practitioner by a compounder outlining the distinct responsibilities of the compounder and practitioner.(y) "Multiple-dose container" means a multiple-unit container for articles or preparations intended for parenteral administration only and usually containing antimicrobial preservatives.(z) "Negative pressure room" means a room that is at a lower pressure than the adjacent spaces and, therefore, the net flow of air is into the room.(aa) "Pharmacy bulk package" means a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture program and are restricted to the preparation of admixtures for infusion or, through a sterile transfer device, for the filling of empty sterile syringes.(ab) "Positive pressure room" means a room that is at a higher pressure than the adjacent spaces and, therefore, the net airflow is out of the room.(ac) "Preparation" means a compounded drug dosage form or dietary supplement or a device to which a compounder has introduced a drug.(ad) "Primary Engineering Control (PEC)" means a device or room that provides an ISO Class 5 environment for the exposure of critical sites when compounding CSPs. Such devices include, but are not limited to, laminar airflow workbenches (LAFWs), BSCs, CAIs, and CACIs.(ae) "Product" means a commercially manufactured sterile drug or nutrient that has been evaluated for safety and efficacy by the FDA.f(af) "Segregated compounding area" means a designated space, either a demarcated area or room, that is restricted to preparing low-risk level CSPs with 12-hour or less BUD. This area shall contain a device that provides unidirectional airflow of ISO Class 5 air quality for preparation of CSPs and shall be oid of activities and materials that are extraneous to sterile compounding.(ag) "Single-dose container" means a single-unit container for articles or preparations intended for parenteral administration only. It is intended for a single use. A single-dose container is labeled as such. Examples of single-dose containers include prefilled syringes, cartridges, fusion-sealed containers, and closure-sealed containers when so labeled.(ah) "Sterilization by Filtration" means passage of a fluid or solution through a sterilizing grade membrane to produce a sterile effluent.(ai) "Sterilizing grade members" means that membranes that are documented to retain 100% of a culture of 107 microorganisms of a strain of Brevundimonas (Psuedomonas) diminuta per square centimeter of membrane surface under a pressure of not less than 30 psi or 2.0 (bar). Such filter membranes are nominally at 0.22-um or 0.2-um nominal pore size, depending on the manufacturer's practice.(aj) "Terminal Sterilization" means the application of a lethal process, such as steam under pressure or autoclaving, to sealed containers for the purpose of achieving a predetermined sterility assurance level of usually less than 10-6, or a probability of less than one in one million of a non-sterile unit.(ak) "Unidirectional flow" means the airflow moving in a single direction in a robust and uniform manner and at a sufficient speed to reproducibly sweep particles away from the critical processing or testing area.(al) "United States Pharmacopia" means a legally recognized compendium of standards for drugs.(am) "Vehicle" means a component for internal and external use that is used as a carrier for diluent in which liquids, semisolids or solids are dissolved or suspended. Examples include, but are not limited to, water, syrups, elixirs, oleaginous liquids, solid and semisolid carriers and proprietary products.N.H. Admin. Code § Ph 404.02
#6181-B, eff 2-5-96, EXPIRED: 2-5-04
New. #8316, eff 3-26-05
Amended by Volume XXXV Number 18, Filed May 7, 2015 , Proposed by #10812, Effective 4/18/2015, Expires 4/18/2025.