Архивы Terminology - Pharma Solutions Ltd

Archiving

Archiving is the process of protecting records from the ability to be further altered or deleted and storing these records under the control of dedicated data management personnel throughout the required records retention period. Archiving is a formal process of taking a record off-line it to a different location disabling it from any further changes.

Lowest published toxic dose

The Lowest published toxic dose (Toxic Dose Low, TDLo) is the lowest dosage per unit of body weight of a substance known to have produced signs of toxicity in a particular animal species. When quoting a TDLo, the particular species and method of administration are typically stated.

Aseptic Processing Room

Aseptic Processing Room - A room in which one or more aseptic activities or processes are performed.

Performance qualification (PQ)

Performance qualification (PQ) should normally follow the successful completion of IQ and OQ. However, it
may in some cases be appropriate to perform it in conjunction with OQ or Process Validation.
PQ should include, but is not limited to the following:
- tests, using production materials, qualified substitutes or simulated product proven to have equivalent behaviour under normal operating conditions with worst-case batch sizes. The frequency of sampling used to confirm process
control should be justified;
- tests should cover the operating range of the intended process unless documented evidence from the development phases confirming the operational ranges is available.

Operational qualification (OQ)

Operational qualification (OQ) normally follows IQ but depending on the complexity of the equipment, it may be performed as a combined Installation/Operation Qualification (IOQ).
OQ should include but is not limited to the following:
- tests that have been developed from the knowledge of processes, systems, and equipment to ensure the system is operating as designed;
- tests to confirm upper and lower operating limits, and /or “worst-case” conditions.
- the completion of a successful OQ should allow the finalization of standard operating and cleaning procedures, operator training and preventative maintenance requirements.

Installation qualification (IQ)

IQ should include, but is not limited to the following:
- Verification of the correct installation of components, instrumentation, equipment, pipework, and services against the engineering drawings and specifications;
- Verification of the correct installation against pre-defined criteria;
- Collection and collation of supplier operating and working instructions and maintenance requirements;
- Calibration of instrumentation;
- Verification of the materials of construction.

Air lock

Air lock - 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.

Action level

Action level - An established microbial or airborne particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation.

Alert Level

Alert Level - An established microbial or airborne particle level giving early warning of potential drift from normal operating conditions and triggers appropriate scrutiny and follow up to address the potential problem. Alert levels are always lower than action levels and are established based on historical and qualification trend data and periodically reviewed.

Barrier

Barrier - A physical partition that affords aseptic processing area (grade A) protection by partially separating it from the surrounding area such as RABS or isolators.

Biological Indicator

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 biological indicator.

Blow-Fill-Seal and form fill seal technology

Blow-Fill-Seal (BFS) technology is a pharmaceutical filling process in which containers are formed from a thermoplastic granulate, filled with product, and then sealed in a continuous, integrated, automatic operation. The two most common types of BFS machines are the Shuttling machine (with Parison cut) and the Rotary machine (Closed Parison) types. The equipment design, operation, and therefore controls for these differ. For Shuttling systems, the processes of container extrusion and filling occur at two separate locations within the machine. The extrusion of the container parison occurs adjacent to the filling zone, the extruded plastic is collected from underneath the extruder head, is cut and formed and automatically transferred (usually by horizontal shuttling) to the filling and sealing zone. For Rotary design machines, the filling needles are enclosed within the extruded parison and therefore there is limited exposure of the inner surfaces of the container to the external environment.

Bioburden

Bioburden - the total number of microorganisms associated with a specific item prior to sterilization.

Bacterial retention testing

Bacterial retention testing – This test is performed to validate that a filter can remove bacteria from a gas or solution. The test is usually performed using a standard organism, such as Brevundimonas diminuta at a minimum concentration of 10 000 000 Colony Forming Units/sq.cm.

Critical area and critical surfaces

Critical area - an area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas such as the grade A area or a closed system.

Commissioning

Commissioning – activities to verify that equipment and systems are installed according to specification.

Colony Forming Unit (cfu)

Colony Forming Unit (cfu) - a microbiological term that describes the formation of a single macroscopic colony after the introduction of one or more microorganisms to microbiological growth media. One colony forming unit is expressed as 1 cfu.

Closed system

Closed system – a system in which the sterile product is not exposed to the surrounding environment.

Clean area

Clean Area - An area with defined particle and microbiological cleanliness standards.

Cleanroom - A room designed, maintained, and controlled to prevent particle and microbiological contamination of drug products. Such a room is assigned and reproducibly meets an appropriate air cleanliness classification.

Clean Non Classified (CNC) area - An area that does not meet any of the formal predetermined grades of cleanliness included in the Annex, i.e. grades A to D, but where a manufacturer defined level of microbial control is still required.

D value

D value - 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.

Dead leg

Deadleg – length of pipe that is not part of the circuit that is greater than 3 internal pipe diameters.

Decontamination vs disinfection

Decontamination - A process that eliminates viable bioburden via use of chemical agents.

Disinfection – The 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.

Dynamic conditions

Dynamic - conditions relating to clean area classification under normal production operations.

Extractables and leachables

Extractables - chemical entities that migrate from the surface of the process equipment contacting with model solvents under appropriate testing conditions (e.g. kind of solvent, temperature) that exceed “worst case” process conditions.

Endotoxin

Endotoxin - 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.

Grade A air

Grade A air – air which is passed through a filter qualified as capable of producing grade A non-viable quality air, but where there is no requirement to continuously perform non-viable monitoring or meet grade A viable monitoring limits.

Gowning qualification

Gowning qualification - a program that establishes, both initially and on a periodic basis, the capability of an individual to do the complete sterile gown in an aseptic manner.

HEPA filter

HEPA filter - high-efficiency particulate air filter with minimum 0.3 μm particle retaining efficiency of 99.97 percent.

Isolator

Isolator - a decontaminated unit supplied with grade A (ISO 5) or higher air quality that provides uncompromised, continuous isolation of its interior from the external environment.

Isokinetic sampling head

Isokinetic sampling head – a sampling head designed to disturb the air as little as possible so that the same particles go into the nozzle as would have passed the area of the nozzle had it not been there.

Intrinsic sterile connection device

Intrinsic sterile connection device - a device that removes the risk of contamination during the connection process; these can be mechanical or fusion devices.

Intervention

Intervention - an aseptic manipulation or activity that occurs in the critical area.

Lyophilization

Lyophilization a physical-chemical drying process designed to remove solvents from both aqueous and non-aqueous systems, primarily to achieve product or material stability.

Laminar and unidirectional flow

Laminar flow - an airflow moving in a single direction and in parallel layers at a constant velocity from the beginning to the end of a straight line vector.

Unidirectional flow - 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.

Overkill sterilization process

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.

Restricted Access Barrier System (RABS)

Restricted Access Barrier System (RABS) - a restricted access barrier system (RABS) provides an enclosed, but not closed, environment meeting defined cleanroom conditions using a rigid-wall enclosure and air overspill to separate its interior from the surrounding environment.

Single-Use Systems

Single-Use Systems (SUS) - Systems in which some product contact components are used only once (i.e. single use components) to replace reusable equipment such as stainless steel transfer lines or bulk containers. SUS covered in this document are those that are used in manufacturing processes of sterile medicinal products (e.g. sterile API, sterile bio bulk, sterile finish dosage), and are typically made up of components such as bags, filters, tubing, connectors, storage bottles, and sensors.

Sterilizing-grade filter

Sterilizing-grade filter - a filter that, when appropriately validated, will remove a defined microbial challenge from a fluid stream, producing a sterile effluent.

Worst case

Worst case - 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.