Gmp terms

Acceptance criteria: the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units).

Action Levels: microbiological levels in the controlled environment, specified in the standard operating procedures, which when exceeded should trigger an investigation and a corrective action based on the investigation.

Air Sampler: devices or equipment used to sample a measured amount of air in a specified time to determine the particulate or microbiological status of air in the controlled environment.

Airborne Particulate Count (or total particulate count): particles detected are 0.3 um, 0.5 um, and larger. when a number of particles is specified, it is the maximum allowable number of particles per cubic meter of air (or per cubic foot of air).

Airborne viable particulate count (or total airborne aerobic microbial count): when a number of microorganisms is specified, it is the maximum number of colony-forming units (cfu) per cubic meter of air (or per cubic foot of air) that is associated with a cleanliness class of controlled environment based on the airborne particulate count.

Airlock : an enclosed space with two or more doors, which is interposed between two or more rooms, e.g., of differing classes of cleanliness. for the purpose of controlling the airflow between those rooms when they need to be entered. an airlock is designed for and used by either people or goods. (27)

Alert Levels : microbial levels, specified in the standard operating procedures, which when exceeded should result in an investigation to ensure that the process is still within control. alert levels are specific for a given facility and are established on the basis of baseline developed under an environmental monitoring program. these alert levels can be modified depending on the trend analysis done in the monitoring program. alert levels are always lower than action levels.

Aseptic Processing: 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 microbiologic critically controlled conditions.

Audit: inspection of facilities, functions, or records.

Authorized person: a person responsible for the release of batches of finished product for sale. in certain countries the batch documentation of a batch of finished product must be signed by an authorized person from the production department and the batch test results by an authorized person from the quality control department for batch release.

batch (or lot): a defined quantity of starting material, packaging material or product processed in a single process or series of processes so that it could he expected to be homogeneous. in the case of continuous manufacture, the batch must correspond to a defined fraction of the production, characterized by its intended homogeneity. it may sometimes be necessary to divide a batch into a number of sub-batches, which are later brought together to form a final homogeneous batch.

Batch Number (or lot number): a distinctive combination of numbers and/or letters which specifically identifies a batch on the labels, the batch records, thecertificates of analysis, etc.

Batch Numbering System: standard operating procedure describing the details of the batch numbering.

Batch Records: all documents associated with the manufacture of a batch of bulk product or finished product. they provide a history of each batch of product and of all circumstances pertinent to the quality of the final product. (27) (in reference 27, batch records for production are called “batch processing records” and for the packaging operations “batch packaging records” )

Bioburden: total number of microorganisms detected in or on an article prior to a sterilization treatment.

Biogenerator: a contained system, such as a fermentor, into which biological agents are introduced along with other materials so as to effect their multiplication or there production of other substances by reaction with the other materials. biogenerators are generally fitted with devices for regulation, control, connection, material addition and material withdrawal. (7) (also called a bioreactor) biological agents: microorganisms, including genetically engineered microorganisms, cell cultures and endoparasites, whether pathogenic or not.

Bulk product: any product that has completed all processing stages up to, but not including, final packaging.

Calibration: the set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling- or the values represented by a material measure, and the corresponding known values of a reference standard. limits for acceptance of the results of measuring should be established.

Cell bank: cell bank system: a cell bank system is a system whereby successive batches of a product are manufactured by culture in cells derived from the same master cell bank [fully characterized for identity and absence of contamination]. a number of containers from the master cell bank are sued to prepare a working cell bank. the cell bank system is validated for a passage level or who/vsq/97.01 105 number of population doublings beyond that achieved during routine production.

Master Cell Bank: a culture of [fully characterized] cells distributed into containers in a single operation, processed together in such a manner as to ensure uniformity and sorted in such a manner as to ensure stability. a master cell bank is usually stored at -70 oc or lower.

Working Cell Bank: a culture of cells derived from the master cell bank intended for use in the preparation of production cell cultures. the working cell bank is usually stored at -70 oc or lower.

Cell Culture: the result from the in-vitro growth isolated from multicellular organisms.

Certification: documented testimaony by qualified authorities that a system qualification, calibration, validation, or revalidation have been performed appropriately and the results are acceptable.

Clean Area: an area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce the introduction generation, and retention of contaminants within the area.

Clean Room: a room in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. in addition, the concentration of microorganisms in the environment is monitored; each cleanliness class defined is also assigned a microbiological level of air, surface, and personnel gear.

Clean/Contained Area: an area constructed and operated in such a manner that will achieve the aims of both a clean area and a contained areas at the same time.

Component: any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product.

Contained Area: an area constructed and operated in such a manner (and equipped with appropriate air handling and filtration) so as to prevent contamination of the external environment by biological agents from within the area.

Containment: the action of confining a biological agent or other entity within a defined space. primary containment: a system of containment which prevents the escape of a biological agent into the immediate working environment. it involves the use of closed containers or safety biological cabinets along with secure operating procedures.

Secondary Containment: a system of containment which prevents the escape of a biological agent into the external environment or into other working areas. it involves the use of rooms with specially designed air handling, the existence of airlocks and/or sterilizers for the exit of materials and secure operating procedures. in many cases it may add to the effectiveness of primary containment.

Control: controls resemble the unknown in composition and are assayed at the same time under the same test conditions by the same method. the results of these tests are used in calculating the mean and standard deviation of the test. controls are used to measure accuracy.

Controlled Environment: any area in an aseptic process system for which airborne particulate and microorganism levels are controlled to specific levels, appropriate to the activities conducted within that environment.

Corrective Action: actions to be performed that are in standard operating procedures and that are triggered by exceeding action levels.

Critical Process: a process that may cause variation in the quality of the pharmaceutical product.

Cross-Contamination: contamination of a starting material. intermediate product, or finished product with another starting material or product during production.

Environmental Isolates: microorganisms that have been isolated from samples from the environmental monitoring program and that represent the microflora of an aseptic processing system.

Environmental Monitoring Program: documented program, implemented through standard operating procedures, that describes in detail the procedures and methods used for monitoring particulates as well as microorganisms in controlled environments (air, surface, personnel gear). the program includes sampling sites, frequency of sampling, and investigative and corrective actions that must be followed if alert or action levels are exceeded. the methodology used for trend analysis is also described.

Finished Product: a product that has undergone all stages of production, including packaging in its final container and labelling.

In-Process Control: checks performed during production in order to monitor and if necessary to adjust the process to ensure that the product conforms to its

Specifications: the control of the environment or equipment may also be regarded as a part of in-process control.

Intermediate Product: partly processed material that must undergo further manufacturing steps before it becomes a bulk product.

Lot: (see terms listed under batch)

Manufacture: all operations of purchase of materials and products, production, quality control, release, storage, shipment of finished products, and the related controls.

Master Formula: a document or set of documents specifying the starting materials with their quantities and the packaging, materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the inprocess controls.

Master Record: a document or set of documents that serve as a basis for the batch

Documentation (blank batch record).

Material Flow: the flow of material and personnel entering controlled environments should follow a specified and documented pathway that has been chosen to reduce or minimize the potential for microbial contamination of the product/closure/container systems. deviation from the prescribed flow could result in increase in potential for microbial contamination. material/personnel flow can changed, but the consequences of the changes from a microbiological who/vsq/97.01 107 point of view should be assessed by responsible managers and must be authorized and documented.

Media Growth Promotion: procedure that references growth promotion under sterility tests to demonstrate that media used in the microbiological environmental monitoring program, or in media-fill runs, are capable of supporting growth of indicator microorganisms and of environmental isolates from samples obtained through the monitoring program.

Packaging Material: any material including printed material employed in the packaging of a pharmaceutical product excluding any outer packaging used for transportation or shipment. packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product.

Procedures: description of the operations to be carried out, the precautions to be taken and measures to be applied directly or indirectly related to the manufacture of a medicinal product.

Process: set of interrelated resources and activities which transform inputs into outputs.

Processing Instructions: see master formula.

Product Contact Areas: areas and surfaces in a controlled environment that are in direct contact with either products, containers, or closures and the microbiological status of which can result in potential microbial contamination of the product/container/closure system. once identified, these areas should be tested more frequently than non-product-contact areas or surfaces.

Production: all operations involved in the preparation of a pharmaceutical product from receipt of materials, through processing and packaging, to completion of the finished product.

Quality Assurance: a wide ranging concept covering all matters that individually or collectively influence the quality of a product. it is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use.

Quality Control: the part of gmp concerned with sampling, specifications, and testing and with the organizations, documentation, and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory.

Quality Management: all activities of the overall management function that determine the quality policy, objectives and responsibilities, and implement them by means such as quality planning, quality control, quality assurance and quality improvement within the quality system.

Quality Policy: overall intentions and direction of an organization with regard to quality, as formally expressed by top management.

Quality: totality of characteristics of an entity that bear on its ability to satisfy stated and implied needs.

Quarantine: the status of starting or packaging materials, intermediates, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection, or reprocessing.

Reconciliation: a comparison, making due allowance for normal variation, between the amount of product or materials theoretically produced or used and the amount actually produced or used.

Record: provide a history of each batch of product, including its distribution, and also of all other relevant circumstances pertinent to the quality of the final product.

Reference Standard: any material of known identity and purity or potency. An official reference standard is one obtained from an official source such as bp, or usp, or who. a house reference standard may be obtained by thorough characterization for identity and purity or potency relative to an official reference standard, or by determination of absolute purity by other techniques. depending on the intended use (qualitative or quantitative) and the nature of the assay, a greater or lesser degree of purity is acceptable.

Sampling Plan: a documented plan that describes the procedures and methods for sampling of a controlled environment, identifies the sampling sites, the frequency and number of samples, that analysis of data, and the interpretation of results.

Sampling Sites: documented geographical location, within a controlled environment, where sampling for microbiological evaluation is taken. in general, sampling sites are selected because of their potential for product/container/ closure contacts.

Seed Lot System: a seed lot system is a system according to which successive batches of a product are derived from the same master seed lot at a given passage level. for routine production, a working seed lot is prepared from the master seed lot. the final product is derived from the working seed lot and has not undergone more passages from the master seed lot than the vaccine shown in clinical studies to be satisfactory with respect to safety and efficacy. the origin and the passage history of the master seed lot and the working seed lot are recorded.

Master Seed Lot: a culture of a micro-organism distributed from a single bulk into containers in a single operation in such a manner as to ensure uniformity, to prevent contamination and to ensure stability. a master seed lot in liquid form is usually stored at or below -70 oc. a freeze-dried master seed lot is stored at a temperature known to ensure stability.

Working Seed Lot: a culture of a micro-organism distributed from the master seed lot and intended for use in production. working seed lots are distributed into containers and stored as described above for master seed lots.

Specification: a document describing in detail the requirements with which the products or materials used or obtained during manufacture have to conform. specifications serve as a basis for quality evaluation.

Standard Operating Procedure (Sop): an authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (e.g., equipment operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection). certain sops may be used to supplement product-specific master and batch production documentation.

Sterility: an acceptably high level of probability that a product processed in an aseptic system does not contain viable microorganisms.

Swabs: devices provided that are used to sample irregular as well as regular surfaces for determination of microbial status. the swab, generally composed of a stick with an absorbent extremity, is moistened before sampling and used to sample a specified unit area of a surface. the swab is then rinsed in sterile saline or other suitable menstruum and the contents plated on nutrient agar plates to obtain an estimate of the viable microbial load on that surface.

System: a regulated pattern of interacting activities and techniques that are united to form an organized whole.

Theoretical Yield: the quantity that would be produced at any appropriate phase of manufacture, processing, or packaging of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production.