Air Changes per Hour
A space of separation between two different air pressures; may be a pass-through chamber or room; a door must be present to prevent loss of pressure in the high pressured room. A small room with interlocked doors, constructed to maintain air pressure control between adjoining rooms (generally with different air cleanliness standards). The intent of an aseptic processing airlock is to preclude ingress of particulate matter and microorganism contamination from a lesser controlled area.
An anteroom between a primary room and corridor ensures a safe airflow buffer zone between the controlled pressurized space and an unclean area. The two spaces are separated by a completely walled area with a door. An ISO Class 8 or better area where personnel may perform hand hygiene and garbing procedures, staging of components, order entry, labeling, and other high particulate generating activities. It is also a transition area that reduces heat and ventilation needs while maintaining positive pressure flow from clean to dirty work areas.
Ante Area or Space
An ante area is a buffer zone of laminar or displacement airflow near a clean work area, such as a pharmaceutical compounding space. There is no physical separation between a gowning or wash area and the compounding area. Instead, proper placement of supply and exhaust airflow devices provides air velocity sufficient to sweep particles away from the compounding area and maintain unidirectional airflow during operations.
A physical partition that affords aseptic processing area (ISO 5) protection by partially separating it from the surrounding area.
Biological Indicator (BI)
A population of microorganisms inoculated onto a suitable medium (e.g., solution, container or closure) and placed within appropriate sterilizer load locations to determine the sterilization cycle efficacy of a physical or chemical process. The challenge microorganism is selected based upon its resistance to the given process. Incoming lot D-value and microbiological count define the quality of the BI.
A type of C-SEC where the C-PEC is located. Cleanroom Buffer Area, Buffer or Core Room, Buffer or Clean Room Areas, Buffer Room Area, Buffer or Clean Area, or Buffer Zone–An ISO Class 7 area where the primary engineering control area is physically located. Activities that occur in this area include the preparation and staging of components and supplies used when compounding sterile preparations.
Biological Safety Cabinet; a ventilated cabinet often used for the preparation of hazardous drugs. Note: there are different classes of BSCs. BSCs support low or medium risk compounded sterile products within a 12-hour or less beyond use date (BUD) or for preparing non-sterile hazardous drugs in a C-PEC.
‘A room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the room and in which other relevant parameters, eg temperature, humidity and pressure are controlled as necessary.’ — ISO 14644-1 Clause 2.1.1
A process, act, or energy that causes materials to be soiled or coated with substances is called contamination. Contamination is distinguished within two categories: film layers and particulates. Electrostatic discharge (ESD) could also be considered as a contaminant.
Feature a building, cell, or room in which the supply, exhaust, and filtration of room air and surface cleanliness is tightly controlled.
Surfaces that may come into contact with or directly affect a sterilized product or its containers or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation, and sterility is maintained throughout processing.
CSP (Compounded Sterile Preparation)
Compounded Sterile Preparation – a sterile drug product that has been prepared by compounding by a qualified individual in a sterile environment. CSPs are not explicitly defined in USP <797>. However, USP <797> does state that certain dosage forms must be sterile when administered to patients.
CAI Compounding Aseptic Isolator (CAI):
An isolator specifically designed for compounding sterile, non-hazardous pharmaceutical ingredients or preparations. A CAI shall not be used for the manipulation of HDs.
Compounding Aseptic Containment Isolator (CACI)
Compounding Aseptic Containment Isolator; a specific type of CAI that is designed for the compounding of sterile hazardous drugs. Ventilated outside of the building. Only a CACI is used for compounding hazardous drugs, not to be confused with a CAI which is only used only for nonhazardous drugs.
Clean Area or Clean Zone
An area with defined particle and microbiological cleanliness standards.
C-PEC (Primary Engineering Control)
Containment Primary Engineering Control; Examples of C-PECs include Class I, II, or III BSCs, CACIs, and CVE. It’s the device in which the compounding will occur. A ventilated device designed and operated to minimize worker and environmental exposures to HDs by controlling emissions of airborne contaminants.
C-PECs used for nonsterile compounding do not need to have ISO Class 5 air quality. C-PECs used for sterile compounding shall have ISO Class 5 air quality.
C-SEC (Secondary Engineering Control)
Containment Secondary Engineering Control; the room in which the C-PEC is placed. The C-SEC is the room in which the C-PEC is placed. It incorporates specific design and operational parameters required to contain the potential hazard within the compounding room (e.g., restricted access, barriers, special construction technique, ventilation, and room pressurization are components of the secondary control strategy).
C-SCA (Containment Segregated Compounding Area)
Containment Segregated Compounding Area; a type of C-SEC. Type of C-SEC with nominal airflow (12 ACPH) and room pressurization requirements (negative pressure between 0.01 0.03 inches of water column) as they pertain to HD compounding. The C-SCA is limited for use with a BSC or CACI when preparing low or medium-risk level CSPs with 12-hour or less BUDs
CVE (Containment Ventilated Enclosure)
A full or partial enclosure that uses ventilation principles to capture, contain, and remove airborne contaminants (through HEPA filtration) and prevent their release into the work environment (e.g., powder hood).
Conditions relating to clean area classification under conditions of normal production.
A process that eliminates viable bioburden via use of sporicidal chemical agents.
Process by which surface bioburden is reduced to a safe level or eliminated. Some disinfection agents are effective only against vegetative microbes, while others possess additional capability to effectively kill bacterial and fungal spores.
A process used to destroy or remove pyrogens (e.g., endotoxin).
The time (in minutes) of exposure at a given temperature that causes a one-log or 90 percent reduction in the population of a specific microorganism.
A pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall.
Endotoxin can lead to reactions in patients receiving injections ranging from fever to death.
A program that establishes, both initially and on a periodic basis, the capability of an individual to don the complete sterile gown in an aseptic manner.
HEPA filter- High efficiency particulate air filter with minimum 0.3 μm particle retaining efficiency of 99.97 percent.
A decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality, that provides uncompromised, continuous isolation of its interior from the external environment (e.g., surrounding cleanroom air and personnel). There are two major types of isolators:
Closed isolator systems exclude external contamination from the isolator’s interior by accomplishing material transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding environment. Closed systems remain sealed throughout operations.
Open isolator systems are designed to allow for the continuous or semi-continuous ingress and/or egress of materials during operations through one or more openings. Openings are engineered (e.g., using continuous overpressure) to exclude the entry of external contamination into the isolator.
Laminar Airflow Workbench (LAFW)
Either a laminar flow clean bench or a biological safety cabinet.
Sterilizing grade filter
A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent.
Any individual participating in the aseptic processing operation, including line set-up, filler, maintenance, or other personnel associated with aseptic line activities.
Overkill sterilization process- A process that is sufficient to provide at least a 12 log reduction of microorganisms having a minimum D value of 1 minute.
A substance that induces a febrile reaction in a patient.
For purposes of this guidance, sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product.
Quality Control Unit
An organizational element with authority and responsibility.
The U.S. Pharmacopeial Convention (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed and consumed worldwide. USP’s drug standards are enforceable in the United States by the Food and Drug Administration, and these standards are used in more than 140 countries.
The United States Pharmacopeia and The National Formulary (USP-NF) is a compilation of drug monographs, biologics, medical devices, dietary supplements, reference tests and standards, and standards for compounding of sterile and non-sterile drug preparations.
The application of a lethal agent to sealed, finished drug products for the purpose of achieving a predetermined sterility assurance level (SAL) of usually less than 10-6 (i.e., a probability of a nonsterile unit of greater than one in a million).
Ultra-low penetration air filter with minimum 0.3 μm particle retaining efficiency of 99.999 percent.
An airflow moving in a single direction, in a robust and uniform manner, and at sufficient speed to reproducibly sweep particles away from the critical processing or testing area.
Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.
A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure.
ISO Class 5 Cleanroom (formerly Class 100)
An atmospheric environment that contains less than 3,520 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 100 particles 0.5 microns in diameter per cubic foot of air).
ISO Class 7 Cleanroom (formerly Class 10,000)
An atmospheric environment that contains less than 352,000 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 10,000 particles 0.5 microns in diameter per cubic foot of air).
ISO Class 8 Cleanroom (formerly Class 100,000)
An atmospheric environment that contains less than 3,520,000 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 100,000 particles 0.5 microns in diameter per cubic foot of air).