PDA Glossary

An established microbial or airborne particle level that, when exceeded, indicates a process is outside of its normal operating range. A response to such an excursion should involve a documented investigation and corrective actions based on the results of that investigation. (TR13)

An established microbial or non-viable particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation. (TR22)

An established microbial or airborne particle level for environmental, water or gas monitoring that, when exceeded, indicates that a facility process is outside of its normal operating range. The response to such an excursion involves a documented investigation and corrective actions based on the results of that investigation. The prescribed action level is often specified in guidance or standards relating to environmental monitoring and water quality. (TR69)

An established microbial or nonviable particle level for environmental, water, or gas monitoring that, when exceeded, indicates a facility or process is outside of its normal operating range. The response to such an excursion may involve a documented investigation and corrective actions based on the results. The prescribed action level is often specified in guidances or standards relating to environmental monitoring and water quality (3-6). (TR88)

The total number of particles of a specific size per unit volume of air. (TR13)

The total number of particles of a specific size per unit volume of air. (TR13)

An established microbial or nonviable particle level giving early warning of potential drift from normal operating conditions; not necessarily grounds for definitive corrective action but typically requires follow-up investigation. (TR13) (TR22) (TR69)

An established level that, when exceeded, is giving an early warning of a potential drift from normal operating conditions; while not necessarily grounds for definitive corrective action, it typically requires follow-up review. (TR 60)

An established microbial or nonviable particle level giving early warning of potential drift from normal operating conditions; not necessarily grounds for definitive corrective action, but typically requires follow-up investigation (3, 4, 7). (TR88)

The part of aseptic processing where a pre- sterilized product is filled and/or packaged into sterile containers and closed. (TR22) (TR28) (TR62) (TR13)

Handling sterile materials in a controlled environment, in which the air supply, facility, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels. (TR28) (TR62) (TR69)

Handling of sterile product, containers, and/ or devices in a controlled environment in which the air supply, materials, equipment, and personnel are regulated to maintain (product) sterility. (TR13)

The total number of microorganisms per unit of material prior to sterilization. (TR13)

Total number of viable microorganisms on or in a health care product prior to sterilization. (TR22)(TR61)(TR62)

A population of viable microorganisms in a fluid prior to sterilizing filtration. (TR26)

A measure of the contaminating organisms found in or on a given amount of material before it undergoes a sterilization process. (TR45) (TR70)

The number of detectable microorganisms (bacteria and fungi) with which an object is contaminated. It is measured in CFU (colony forming units). (TR47)

The number of viable, contaminating microorganisms present on a product immediately prior to decontamination. (TR51)

Viable microbial contaminants associated with personnel manufacturing environments (air and surfaces), equipment, product packaging, raw materials (including water), in-process materials, and finished products. (TR 67) (TR 69)

A series of consecutive production batches manufactured without intervening cleaning and sterilization. (TR13) (TR22) (TR62)

Processing of multiple lots or batches of the same product serially in the same equipment. (TR29) (TR49)

The process of removing foulants from the membrane structure during normal processing, either through physical or chemical means. (TR13) (TR15)

The removal of adherent visible soil from the surfaces, crevices, serrations, joints, and lumens of instruments, and from devices and equipment, by a manual or mechanical process that prepares the items for safe handling and/or further decontamination. The cleaning process should leave surfaces that are visibly free from foreign material. (TR51)

A room designed, maintained, and controlled to prevent particle and microbiological contamination of a drug product or medical device. A cleanroom is assigned and reproducibly meets an appropriate air cleanliness classification. (TR13)

A mechanism by which temperature is regulated and recorded without interruption. It is recommended that if the system is not alarmed, it must be checked at predetermined time intervals. The time intervals should be determined by the facility but should be adequate enough to provide meaningful data of the temperature change over time. (TR46)

A process of data collection in which conditions are monitored continuously throughout the operation. In most U.S. applications, this definition implies “during production.” (TR13)

An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination (an air supply approximating to Grade D may be appropriate), and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure positive to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. (TR13)

Actions taken to eliminate the cause of an existing (corrective) or potential (preventative) non-conformity to prevent its recurrence. (TR52)

Action to eliminate the cause of a detected non-conformity or other undesirable situation. (TR54)

A response taken to remediate the effect of an excursion or product failure. (TR13)

Action taken to eliminate the causes of an existing deviation or other undesirable situation to prevent recurrence. (TR88)

An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas. (TR13) (TR22) (TR44) (TR62)

A surface within a critical area that may come in direct contact with sterilized products, containers, or closures. (TR13)

The destruction of pathogenic and other kinds of microorganisms by thermal or chemical means. (TR51) (TR70)

Process of eliminating nearly all recognized pathogenic microorganisms but not necessarily all microbial forms (e.g., bacterial spores) on inanimate objects. (TR69)

The chemical or physical inactivation of a bioburden on inanimate surfaces. Typically this requires a minimum three-log (3-log) reduction of vegetative microorganisms and two-log (2-log) reduction for bacterial spore be achieved in validation. (TR13)

The time in minutes required for a one-logarithm, or 90%, reduction of the population of microorganisms used as a biological indicator under specified lethal conditions. For dry-heat sterilization, the D-value should always be specified with a reference temperature, DT. For example, a biological indicator (BI) challenge system with a D 160°C=1.9 minutes, requires 1.9 minutes at 160°C to reduce the population by one logarithm. (TR3)

The time in minutes at a specific temperature required to reduce the population of a specific microorganism by 90% [or one (1) log] in defined conditions [e.g., method of sterilization (dry heat versus

steam), solute, or carrier]. (TR13)

Monitoring of an environment during normal operations, that is, when the usual equipment is operating and personnel are present, and the process or simulated process is ongoing. Per the EU and ISO documents this is synonymous with operational condition (including the equipment operating and personnel present). (TR13)

Conditions and corresponding measurements as associated with facilities and equipment used in the control of a manufacturing area that may impact the identity, strength, quality, or purity of a product. Among such parameters are airflow rates and patterns, pressure differentials, materials and personnel flow, temperature and relative humidity, as well as nonviable and viable particulates. (TR13)

A process of collecting data in which conditions are monitored at a defined frequency not exceeding sixty minutes during operation. In most U.S. applications, this means “during production.” (TR13)

A process of dividing areas of equivalent classifications into grids for the purpose of uniformly assessing contamination characteristics in that area.This process is usually confined to the validation of new facilities and not routine monitoring. (TR13)

A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous, isolation of its interior from the surrounding environment. Any air exchange with the surrounding environment takes place only through microbially retentive filters. (TR22) (TR62) (TR13)

A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous, isolation of its interior from the surrounding environment. It may transfer air directly to the surrounding environment through openings (e.g., “mouse holes”) that preclude the ingress of microbial contamination. (TR13) (TR22) (TR62)

The description of microorganisms based on their cellular morphology, Gram reaction, and key diagnostic tests (e.g., Gram-positive coagulase-negative cocci). (TR13)

The arrangement of microorganisms into taxonomic groups based on their similarities and relationships. (TR13)

The determination of the genus, and species when possible, to which a laboratory or manufacturing isolate belongs. (TR13)

A term used in reference to particulates that are not capable of living, growing, or developing and functioning successfully (“unable to divide” or “not capable of reproducing”). (TR13)

A sterility release system based upon effective control, monitoring, documentation, and batch records review of a validated sterilization process cycle in lieu of release procedures based upon end-product sterility testing. (TR01) (TR3) (TR13)

A sterility release program based on effective control, monitoring and documentation of a validated sterile-product manufacturing process where sterility release is based on demonstrated achievement of critical operational parameters and performance attributes in lieu of end-product sterility testing. (TR30)

Conditions and corresponding measurements associated with the manufacturing process that may affect the identity, strength, quality, potency, and purity of a product. Examples of parameters of concern include bioburden, process rate, weight, volume, temperature, and pressure. (TR13)

RABS are aseptic processing systems (ISO 5) intended to substantially reduce human borne contamination within the aseptic environment where sterile product, containers, closures and equipment are exposed by the use of separative devices and defined mechanical features and operating procedures. (TR22) (TR62)

Aseptic processing systems (ISO 5) intended to substantially reduce human-borne contamination within the aseptic environment where sterile product, containers, closures, and equipment are exposed by the use of separative devices and defined mechanical features and operating procedures. (TR13)

Reduction of microbial contaminants to safe levels as judged by public health requirements for the specific country. (TR13)

A significant reduction in bioburden, achieved in chromatography by the use of bactericidal agents, such as sodium hydroxide (NaOH), hydrochloric acid (HCl), ethanol (EtOH), and isopropanol (IPA). (TR14)

The process of reducing microbial levels by treatment at less than defined sterilizing conditions. Typically water at 80 °C or a chemical treatment is used to perform sanitization of process components. (TR45)

A process that reduces the number of viable microorganisms to a defined level. (TR61) (TR69)

A bacterial dormant form that is highly resistant to adverse conditions. Fungal spores are not highly resistant; their susceptibilities are closer to vegetative microorganisms. (TR13)

Monitoring of the environment in the absence of normal operations. This includes having the equipment installed and operational when no personnel are present. Per the EU and ISO standards, this is synonymous with “at rest.” (TR13)

A process used to render a product free of viable organisms with a specified probability. (TR01) (TR30) (TR69)

A process by which something is rendered sterile (i.e., moist heat, dry heat, chemical, irradiation); normally validated at 10⁶ organism reduction. (TR70)

Validated process used to render product free from viable microorganisms (TR13) (TR26)

A specific isolate of a species that is maintained in pure culture and is serotypically, genotypically, or chemotaxonomically characterized to differentiate it from other strains of the same species. The strain is representative of the species and provides a reference for the species based on its historic isolation, characterization, and deposition in recognized culture collections. (TR13)

A process whereby product is sterilized within its sterile barrier system. (TR01

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 less than one in a million). A process where the material is sterilized in its final packaged configuration. (TR13)

Analysis of environmental data over time indicating a shift; adverse trends require investigation. (TR70)

A review performed in response to an alert or action condition. This review provides an analysis of specific environmental monitoring data to identify adverse trends.(TR13)

Cells in an actively growing state. Some microorganisms can only be vegetative, while others are sporeformers and can be in a vegetative or spore (dormant) state. (TR13)