C
Calibration
The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard.
[EU GMP Guide, Glossary, PIC/S PE 010-4]
The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements. [EU GMP Guide, Part II, ICH Q7]
(étalonnage) Set of tests that confirms under desired conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding values of a reference standard. [Canadian GMP Guidelines 2009, Annex 5]
Campaigned Manufacture
The manufacture of a series of batches of the same product in sequence in a given period of time followed by strict adherence to accepted control measures before transfer to another product. The products are not run at the same time but may be run on the same equipment. [EU GMP Guide, Annex 2]
CAPA (Corrective and Preventive Action)
A systematic approach that includes actions needed to correct (“correction”), prevent recurrence (“corrective action”), and eliminate the cause of potential nonconforming product and other quality problems (preventive action). [21 CFR 820, FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Capability of a Process
Ability of a process to realise a product that will fulfil the requirements of that product. The concept of process capability can also be defined in statistical terms. [ISO 9000:2005, ICH Q10]
Carrier
A stable element present with a radionuclide of the same element. [Canadian GMP Guidelines, Annex 5]
A stable element that is added, in detectable quantities, to a radionuclide of the same element, usually to facilitate processing of the radionuclide. [Canadian GMP Guidelines, Annex 3]
Catalyst
(catalyseur) A substance usually used in small amounts relative to the reactants that modifies and increases the rate of a reaction without being consumed in the process. [Canadian GMP Guidelines, Annex 5]
Cell Bank
(see also Working 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. A number of containers from the master cell bank are used to prepare a working cell bank. The cell bank system is validated for a passage level or number of population doublings beyond that achieved during routine production. Master cell bank: A culture of [fully characterised] cells distributed into containers in a single operation, processed together in such a manner as to ensure uniformity and stored in such a manner as to ensure stability. A master cell bank is usually stored at -70 °C or lower. Working cell bank: A culture of cells derived from the master cell bank and intended for use in the preparation of production cell cultures. The working cell bank is usually stored at -70°C or lower. [EU GMP Guide, Glossary]
A collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. Each container represents an aliquot of a single pool of cells. [EU GMP Guide, Annex 2]
A cell bank is a collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. Each container represents an aliquot of a single pool of cells. [ICH Q5D, Canadian GMP Guidelines 2009, Annex 2]
Cell Culture
The result from the in-vitro growth of cells isolated from multicellular organisms. [EU GMP Guide, Glossary]
(culture cellulaire) Maintenance or propagation of cells in vitro. Cell culture is performed according to good aseptic/sterile techniques to ensure the absence of microbial contamination. [Canadian GMP Guidelines 2009, Annex 2]
Cell Line
Type of cell population which originates by serial subculture of a primary cell population, which can be banked. [ICH Q5D]
Cell Stock
Primary cells expanded to a given number of cells to be aliquoted and used as starting material for production of a limited number of lots of a cell based medicinal product. [EU GMP Guide, Annex 2]
Cell Substrate
Cells used to manufacture product. [ICH Q5A]
Certificate of Analysis (COA)
A document containing the name and address of the laboratory performing the test(s), name and specifications of the material(s), test(s) performed, test method(s) used, actual numerical results, approval date(s), signature of approver, and any other technical information deemed necessary for its proper use. [Canadian GMP Guidelines 2009]
Certificate of Compliance (CoC)
(certificat de conformité (CC)) A certificate issued by a Regulatory Authority attesting to the GMP compliance of a recognized building in that country. In Canada, the CoC is issued by the HPFB Inspectorate. [Canadian GMP Guidelines 2009]
Certificate of Manufacture
(certificat de fabrication) A document issued by a vendor to a distributor or importer that attests that a specific lot or batch of drug has been produced in accordance with its master production documents. Such certificates include a detailed summary of current batch documentation, with reference to respective dates of revision, manufacture, and packaging, and are signed and dated by the vendor’s quality control department. For drugs that are fabricated, packaged/labelled and tested in MRA countries, the batch certificate is considered to be equivalent. [Canadian GMP Guidelines 2009]
Certificate of Pharmaceutcial Product (CPP)
A certificate issued by the Inspectorate establishing the regulatory status of the pharmaceutical, biological, radiopharmaceutical or veterinary product listed and the GMP status of the fabricator of the product. This certificate is in the format recommended by the WHO. [Canadian GMP Guidelines 2009]
Certification of the Finished Product Batch
The certification in a register or equivalent document by a Qualified Person (QP), as defined in Article 51 of Directive 2001/83/EC and Article 55 of Directive 2001/82/EC, before a batch is released for sale or distribution. [EU GMP Guide, Annex 16]
Change Control
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure that the system is maintained in a validated state. [EU GMP Guide, Annex15, PIC/S PI 011-3]
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state. [Main Principles for Pharmaceutical Products, WHO, PIC/S PI 006-3]
A written procedure that describes the action to be taken if a change is proposed
(a) to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and testing of drugs, or
(b) that may affect the operation of the quality or support system.
[Canadian GMP Guidelines 2009]
Change Management
A systematic approach to proposing, evaluating, approving, implementing and reviewing changes. [ICH Q10]
A less formal approach to change control that is generally utilised during the preliminary planning and design stage of a project. (Many companies will elect to move straight to a change control system in a design stage of a complex project. This has the advantage of formality, more accurate records and documentation as well as a strong traceability and accountability feature). [PIC/S PI 006-3]
Changeover Procedure
(procédure de conversion) A logical series of validated steps that ensures the proper cleaning of suites and equipment before the processing of a different product begins. [Canadian GMP Guidelines 2009]
Chemical Development Studies
Studies conducted to scale-up, optimize, and validate the manufacturing process for a new drug substance. [ICH Q3A]
Chemical Transformation Step
For Chemical Entities, a step involved in the synthesis of the chemical structure of the drug substance from precursor molecular fragments. Typically it involves C-X or C-C bond formation or breaking. [ICH Q11]
Chiral
Not super imposable with its mirror image, as applied to molecules, conformations, and macroscopic objects, such as crystals. The term has been extended to samples of substances whose molecules are chiral, even if the macroscopic assembly of such molecules is racemic. [ICH Q6A]
Classical Fermentation
The term "classical fermentation" refers to processes that use microorganisms existing in nature and/or modified by conventional methods (e.g. irradiation or chemical mutagenesis) to produce APIs. APIs produced by "classical fermentation" are normally low molecular weight products such as antibiotics, amino acids, vitamins, and carbohydrates. [Chinese GMP Guidelines, Annex 2]
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. Note: The different degrees of environmental control are defined in the Supplementary Guidelines for the Manufacture of sterile medicinal products. [EU GMP Guide, Glossary]
An area (or room) 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. [Main Principles for Pharmaceutical Products, WHO]
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. [PIC/S PE 010-4]
An area with defined particle and microbiological cleanliness standards. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
(aire propre) A room or suite of rooms where Grade C or D conditions (see table in Section C.02.029 of these guidelines) are required. The rooms have a defined environmental control of particulate and microbial contamination and are constructed, maintained, and used in such a way as to minimize the introduction, generation, and retention of contaminants. [Canadian GMP Guidelines 2009]
Throughout this Ministerial Ordinance means the place, among those areas where the manufacturing operations are conducted (hereinafter referred to as “work areas”), where the weighing operations for the raw materials or the formulating operations for the drug substances are conducted or where the cleaned containers are exposed to the air in the work areas. [Japan MHLW Ministerial Ordinance No. 179, 2004]
Cleaning Validation
Cleaning validation is documented evidence that an approved cleaning procedure will provide equipment which is suitable for processing medicinal products. [EU GMP Guide, Annex 15]
Documented evidence to establish that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration factors such as batch size, dosing, toxicology and equipment size. [Main Principles for Pharmaceutical Products, WHO]
Documented evidence that an approved cleaning procedure will provide equipment which is suitable for processing of pharmaceutical products or active pharmaceutical ingredients (APIs). [PIC/S PI 006-3]
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Clinical Trial
Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s) and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of one or more investigational medicinal product(s) with the object of ascertaining its/their safety and/or efficacy. [EU GMP Guide, Annex 13]
Closed Isolator System
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Closed Procedure
A procedure whereby a sterile pharmaceutical product is prepared by transferring sterile ingredients or solutions to a pre-sterilised sealed container, either directly or using a sterile transfer device, without exposing the solution to the external environment. [PIC/S PE 010-4]
Closed System
Where a drug substance or product is not exposed to the immediate room environment during manufacture. [EU GMP Guide, Annex 2]
A system for collecting and/or processing blood in containers that have been connected together before sterilization, so that there is no possibility of microbial contamination from outside after collection of blood from the donor. [Canadian GMP Guidelines, Annex 14]
Cold Chain
(chaîne du froid) Maintenance of a designated temperature throughout the manufacturing process and during storage, until the product is used. [Canadian GMP Guidelines, Annex 2]
Colony Forming Units (CFU)
Visible outcome of growth of micro-organisms arising from a single or multiple cells. [PIC/S PI 012-3]
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Combination Product
A drug product which contains more than one drug substance [ICH Q6A]
Commercial Off-the-Shelf (COTS)
Configurable programs – stock programs that can be configured to specific user applications by “filling in the blanks”, without (COTS) altering the basic program. [PIC/S PI 011-3]
Commissioning
An engineering term that covers all aspects of bringing a system or sub-system to a position where it is regarded as being ready for use in pharmaceutical manufacture. Commissioning involves all the basis requirements of Installation Qualification (IQ) and Operational Qualification (OQ). [PIC/S PI 006-3]
The setting up, adjustment and testing of equipment or a system to ensure that it meets all the requirements, as specified in the user requirement specification, and capacities as specified by the designer or developer. Commissioning is carried out before qualification and validation. [TRS 961 Annex 7, WHO]
Commitment Batch
(lots de fabrication visés pour des essais systématiques) Production batches of a drug substance or drug product for which the stability studies are initiated or completed post approval through a commitment made in the registration application. [ICH Q1A, Canadian GMP Guidelines 2009]
Common Name
The international non-proprietary name recommended by the World Health Organization, or, if one does not exist, the usual common name. [Directive 2001/83/EC]
Comparability Bridging Study
A study performed to provide nonclinical or clinical data that allows extrapolation of the existing data from the drug product produced by the current process to the drug product from the changed process. [ICH Q5E]
Comparability Exercise
The activities, including study design, conduct of studies, and evaluation of data, that are designed to investigate whether the products are comparable. [ICH Q5E]
Comparable
A conclusion that products have highly similar quality attributes before and after manufacturing process changes and that no adverse impact on the safety or efficacy, including immunogenicity, of the drug product occurred. This conclusion can be based on an analysis of product quality attributes. In some cases, nonclinical or clinical data might contribute to the conclusion. [ICH Q5E]
Comparator Product
(médicament de comparaison) An investigational or marketed product (i.e. active control), or placebo, used as a reference in a clinical trial. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Complaint
Any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a [medical] device after it is released for distribution. [21 CFR Part 820, FDA]
Component
Any ingredient intended for use in the manufacture of a drug product, including those that may not appear in the final drug product.
[Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA, Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA, 21 CFR Part 210, FDA]
Any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled [medical] device. [21 CFR Part 820, FDA]
A unit of a drug, other than a radionuclide, separately packaged in a kit for use in the preparation of a radiopharmaceutical, or an empty vial or other accessory item in a kit. [Canadian GMP Guidelines 2009, Annex 3]
Compounding
A process wherein bulk drug substance is combined with another bulk drug substance and/or one or more excipients to produce a drug product. [PIC/S PI 007-6]
Compressed Gas
Gas which, when packaged under pressure for transport, is entirely gaseous at all temperatures above –50 °C. [EU GMP Guide, Annex 6]
Computer Hardware
Various pieces of equipment in the computer system, including the central processing unit, the printer, the modem, the cathode ray tube (CRT), and other related apparatus. [PIC/S PI 011-3]
Computer System
A group of hardware components and associated software, designed and assembled to perform a specific function or group of functions. [EU GMP Guide, Part II, ICH Q7]
Computer hardware components assembled to perform in conjunction with a set of software programs, which are collectively designed to perform a specific function or group of functions. [PIC/S PI 011-3]
Computerised System
A system including the input of data, electronic processing and the output of information to be used either for reporting or automatic control. [EU GMP Guide, Glossary]
A process or operation integrated with a computer system. [EU GMP Guide, Part II, ICH Q7]
A computer system plus the controlled function that it operates. [Authors note: Today this may be considered to be rather a narrow definition, especially in the context of integrated computers. The definition should therefore include all outside influences that interface with the computer system in its operating environment. These may typically include monitoring and network links, (to/from other systems or instruments), manual (keypad inputs), links to different media, manual procedures and automation. The term also covers automated instruments and systems. See also the definition for ‘automated systems’ in this section and Section 26, Reference 11, the GLP OECD consensus document. PIC/S GMP Annex 11(4) is relevant here regarding documenting the scope and interaction of systems.] [PIC/S PI 011-3]
Concurrent Production
(production simultanée) Simultaneous processing of more than one product in the same room/suite of a multi-product facility, or simultaneous processing of more than one lot of a product in a dedicated facility. [Canadian GMP Guidelines, Annex 2]
Concurrent Release
Releasing for distribution a lot of finished product, manufactured following a qualification protocol, that meets the lot release criteria established in the protocol, but before the entire study protocol has been executed [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Concurrent Validation
Validation carried out in exceptional circumstances, justified on the basis of significant patient benefit, where the validation protocol is executed concurrently with commercialisation of the validation batches. [EU GMP Guide, Annex 15]
Validation carried out during routine production of products intended for sale. [PIC/S PI 006-3]
Confidential Unit Exclusion (CUE)
A system that allows the donor, in private, to indicate that his/her collected blood should, or should not, be used for transfusion to another individual.
[Canadian GMP Guide, Annex 14]
Configuration
The documented physical and functional characteristics of a particular item, or system, e.g. software, computerised system, hardware, firmware and operating system. A change converts one configuration into a new one. [PIC/S PI 011-3]
Configuration Management
The process of identifying and defining the configuration items in a system, controlling the release and change of these items throughout the system life cycle, recording and reporting the status of configuration items and change requests, and verifying the completeness and correctness of configuration items. [PIC/S PI 011-3]
Confirmation
A signed statement that a process or test has been conducted in accordance with GMP and the relevant marketing authorisation, as agreed in writing with the Qualified Person responsible for certifying the finished product batch before release. Confirm and confirmed have equivalent meanings.
[EU GMP Guide, Annex 16]
Confirmatory Studies
Studies undertaken to establish photostability characteristics under standardized conditions. These studies are used to identify precautionary measures needed in manufacturing or formulation and whether light resistant packaging and/or special labeling is needed to mitigate exposure to light. For the confirmatory studies, the batch(es) should be selected according to batch selection for long-term and accelerated testings which is described in the Parent Guideline. [ICH Q1B]
Conjugated Product
A conjugated product is made up of an active ingredient (for example, peptide, carbohydrate) bound covalently or noncovalently to a carrier (for example, protein, peptide, inorganic mineral) with the objective of improving the efficacy or stability of the product. [ICH Q5C]
Consignment
The quantity of a pharmaceutical(s), made by one manufacturer and supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include material belonging to more than one batch. [Main Principles for Pharmaceutical Products, WHO]
The quantity of pharmaceutical products supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include pharmaceutical products belonging to more than one batch. [Good Distribution Practices for Pharmaceutical Products, WHO]
The quantity of a bulk starting material, or of a drug product, made by one manufacturer or supplied by an agent, and supplied at one time in response to a particular request or order. A consignment may comprise one or more lot-identified packages or containers and may include material belonging to more than one lot-identified batch. [Sampling Operations, WHO]
Constituent with Known Therapeutic Activity
Substances or groups of substances which are chemically defined and known to contribute to the therapeutic activity of a herbal material or of a preparation. [Good Manufacturing Practices: Specific Pharmaceutical Products, WHO]
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. [EU GMP Guide, Glossary]
Container
A container is a cryogenic vessel (tank, tanker or other type of mobile cryogenic vessel) a cylinder, a cylinder bundle or any other package that is in direct contact with the gas. [EU GMP Guide, Annex 6]
The material employed in the packaging of a pharmaceutical product. Containers include primary, secondary and transportation containers. Containers are referred to as primary if they are intended to be in direct contact with the product. Secondary containers are not intended to be in direct contact with the product. [Good Distribution Practices for Pharmaceutical Products, WHO]
Container Closure System
The sum of packaging components that together contain and protect the dosage form. This includes primary packaging components and secondary packaging components, if the latter are intended to provide additional protection to the drug product. A packaging system is equivalent to a container closure system. [ICH Q1A]
Containment
The action of confining a biological agent or other entity within a defined space. [EU GMP Guide, Glossary]
A process or device to contain product, dust or contaminants in one zone, preventing it from escaping to another zone. [TRS 957 Annex 5, WHO]
(confinement) Total isolation of one or more steps of a manufacturing process to prevent cross-contamination of the product, or staff, from all other steps of the process. [Canadian GMP Guidelines 2009, Annex 2]
(primary)
EA 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. [EU GMP Guide, Glossary]
(secondary)
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 sterilisers for the exit of materials and secure operating procedures. In many cases it may add to the effectiveness of primary containment. [EU GMP Guide, Glossary]
Contaminant
Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not intended to be part of the manufacturing process of the drug substance or drug product. [ICH Q6B]
Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, inter mediate, or API during production, sampling, packaging or repackaging, storage or transport. [EU GMP Guide, Part II, ICH Q7]
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a starting material, or intermediate or finished product during production, sampling, packaging or repackaging, storage or transport. [Guide to good storage practices for pharmaceuticals, WHO]
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, in-process material, or phase 1 investigational drug during manufacturing, sampling, packaging or repackaging, storage, or transport. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Continous Cell Line
A cell line having an infinite capacity for growth. Often referred to as "“immortal”" and previously referred to as “established”. [ICH Q5D]
Continous Culture
(culture en continu) Process by which growth of cells is maintained by periodically replacing a portion of the cells and medium such that there is no lag or saturation phase. [Canadian GMP Guidelines, Annex 2]
Continous Process Verification
An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. [ICH Q8]
Continual Improvement
Recurring activity to increase the ability to fulfil requirements. (ISO 9000:2005). [ICH Q10]
Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Contract Facility
Organisation performing work associated with the manufacturing process for the manufacturer. [Canadian GMP Guide, Annex 14]
Contract Manufacturer
A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer. [EU GMP Guide, Part II, ICH Q7]
Control Measure
Any action and activity that can be used to prevent or eliminate a pharmaceutical quality hazard or reduce it to an acceptable level. [Hazard and Risk Analysis, WHO]
Control Number
see Batch Number
Control Strategy
A planned set of controls, derived from current product and process understanding, that assures process performance and product quality. The controls can include
parameters and attribtues related to drug substance and drug product materials and components,
facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. [ICH Q10]
Controlled Area
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 negative to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. [EU GMP Guide, Glossary]
Controlled Work Area
An enclosed work area constructed and operated in such a manner and equipped with appropriate air handling and filtration systems to reduce to a pre-defined level the introduction, generation and retention of contaminants. A controlled work area may also be used to protect the external environment from the materials being handled in it e.g. vaccines or cytotoxics. [PIC/S PE 010-4]
Correction
Repair, rework, or adjustment relating to the disposition of an existing discrepancy. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Action to eliminate a detected non-conformity. Note 1: There is a distinction between correction and corrective action. A correction can be made in conjunction with a corrective action. Note 2: A correction can be, for example, rework or reclassification. [ISO 9000:2005]
Corrective Action (CA)
Action to eliminate the cause of a detected non-conformity or other undesirable situation. NOTE: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the causes of an existing discrepancy or other undesirable situation to prevent recurrence. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Corrective Action and Preventive Action
see CAPA
COTS
see Commercial Off-the-Shelf
Counterfeit Pharmaceutical Product
A pharmaceutical product which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products, and counterfeit pharmaceutical products may include products with the correct ingredients, with the wrong ingredients, without active ingredients, with an incorrect quantity of active ingredient or with fake packaging. [Good Distribution Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Critical
Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification. [EU GMP Guide, Part II, ICH Q7]
Critical Area / Critical Zone
That part of the controlled work area where containers are opened and the product is exposed. Particulate and microbiological contamination should be reduced to levels appropriate to the intended use. [PIC/S PE 010-4]
Zone within the Aseptic Processing Area where sterile product, product components or product contact surfaces are exposed to the environment. [PIC/S PE 014-4]
An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas. [FDA Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP]
Area in which the sterilized drug product, containers, and closures are exposed to environmental conditions that must be designed to maintain product sterility. Activities conducted in this area include manipulations, such as aseptic connections, sterile ingredient additions, filling and closing operations. [Canadian GMP Guidelines 2009]
Critical Control Point(CCP)
A step at which control can be applied and is essential to prevent or eliminate a pharmaceutical quality hazard or to reduce it to an acceptable level. [TRS 961 Annex 7, WHO]
Critical Labelling
Labelling which identifies a product or status, such as a quarantine label or blood group label, if it is used to control release for inventory. [Canadian GMP Guidelines, Annex 14]
Critical Operation
An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical product. [Main Principles for Pharmaceutical Products, WHO]
Critical Process Parameter (CPP)
A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. [ICH Q8]
Critical Quality Attribute (CQA)
A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. [ICH Q8]
This refers to attributes of physical, chemical, biological or microorganism, should be of certain limits, scope or distribution, so as to meet expectant product quality. [Chinese GMP Guidelines, Annex 2]
Critical Surface
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Critical Variable Study
A study that serves to measure variables (parameters) critical to the satisfactory operation of a piece of equipment or plant and to assure their operation within monitored and controlled limits. Examples of variables would be pressure, temperature, flow rates, time etc. [PIC/S PI 006-3]
Cross-Contamination
Contamination of a material or of a product with another material or product. [EU GMP Guide Part I, Glossary, ICH Q7, PIC/S PE 010-4]
Contamination of a starting material, intermediate product or finished product with another starting material or product during production. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Contamination of a material or phase 1 investigational drug with another material or product. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Contamination of a drug or biological starting material or in-process intermediate with another drug or biological starting material or in-process intermediate. In multi-product facilities, cross-contamination can occur throughout the manufacturing process, from generation of the MCB and WCB through finishing. [Canadian GMP Guidelines 2009, Annex 2]
Crude Plant/Vegetable Drug
Fresh or dried medicinal plant or parts thereof. [EU GMP Guide, Glossary]
Customer
A person or organization (internal or external) that receives a product or service anywhere along the product’s life cycle.
[Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Cylinder
A container designed to contain gas at a high pressure. [EU GMP Guide, Glossary]
Container usually cylindrical suited for compressed, liquefied or dissolved gas, fitted with a device to regulate the spontaneous outflow of gas at atmospheric pressure and room temperature. [EU GMP Guide, Annex 6]
Cylinder Bundle
An assembly of cylinders that are fastened together, interconnected by a manifold and transported and used as a unit. [EU GMP Guide, Annex 6]
Cyrogenic Gas
A gas which liquefies at 1.013 bar at temperatures below -150 °C. [EU GMP Guide, Annex 6]
Cyrogenic Vessel
A container designed to contain liquefied gas at extremely low temperature. [EU GMP Guide, Glossary]
The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard.
[EU GMP Guide, Glossary, PIC/S PE 010-4]
The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements. [EU GMP Guide, Part II, ICH Q7]
(étalonnage) Set of tests that confirms under desired conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding values of a reference standard. [Canadian GMP Guidelines 2009, Annex 5]
Campaigned Manufacture
The manufacture of a series of batches of the same product in sequence in a given period of time followed by strict adherence to accepted control measures before transfer to another product. The products are not run at the same time but may be run on the same equipment. [EU GMP Guide, Annex 2]
CAPA (Corrective and Preventive Action)
A systematic approach that includes actions needed to correct (“correction”), prevent recurrence (“corrective action”), and eliminate the cause of potential nonconforming product and other quality problems (preventive action). [21 CFR 820, FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Capability of a Process
Ability of a process to realise a product that will fulfil the requirements of that product. The concept of process capability can also be defined in statistical terms. [ISO 9000:2005, ICH Q10]
Carrier
A stable element present with a radionuclide of the same element. [Canadian GMP Guidelines, Annex 5]
A stable element that is added, in detectable quantities, to a radionuclide of the same element, usually to facilitate processing of the radionuclide. [Canadian GMP Guidelines, Annex 3]
Catalyst
(catalyseur) A substance usually used in small amounts relative to the reactants that modifies and increases the rate of a reaction without being consumed in the process. [Canadian GMP Guidelines, Annex 5]
Cell Bank
(see also Working 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. A number of containers from the master cell bank are used to prepare a working cell bank. The cell bank system is validated for a passage level or number of population doublings beyond that achieved during routine production. Master cell bank: A culture of [fully characterised] cells distributed into containers in a single operation, processed together in such a manner as to ensure uniformity and stored in such a manner as to ensure stability. A master cell bank is usually stored at -70 °C or lower. Working cell bank: A culture of cells derived from the master cell bank and intended for use in the preparation of production cell cultures. The working cell bank is usually stored at -70°C or lower. [EU GMP Guide, Glossary]
A collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. Each container represents an aliquot of a single pool of cells. [EU GMP Guide, Annex 2]
A cell bank is a collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. Each container represents an aliquot of a single pool of cells. [ICH Q5D, Canadian GMP Guidelines 2009, Annex 2]
Cell Culture
The result from the in-vitro growth of cells isolated from multicellular organisms. [EU GMP Guide, Glossary]
(culture cellulaire) Maintenance or propagation of cells in vitro. Cell culture is performed according to good aseptic/sterile techniques to ensure the absence of microbial contamination. [Canadian GMP Guidelines 2009, Annex 2]
Cell Line
Type of cell population which originates by serial subculture of a primary cell population, which can be banked. [ICH Q5D]
Cell Stock
Primary cells expanded to a given number of cells to be aliquoted and used as starting material for production of a limited number of lots of a cell based medicinal product. [EU GMP Guide, Annex 2]
Cell Substrate
Cells used to manufacture product. [ICH Q5A]
Certificate of Analysis (COA)
A document containing the name and address of the laboratory performing the test(s), name and specifications of the material(s), test(s) performed, test method(s) used, actual numerical results, approval date(s), signature of approver, and any other technical information deemed necessary for its proper use. [Canadian GMP Guidelines 2009]
Certificate of Compliance (CoC)
(certificat de conformité (CC)) A certificate issued by a Regulatory Authority attesting to the GMP compliance of a recognized building in that country. In Canada, the CoC is issued by the HPFB Inspectorate. [Canadian GMP Guidelines 2009]
Certificate of Manufacture
(certificat de fabrication) A document issued by a vendor to a distributor or importer that attests that a specific lot or batch of drug has been produced in accordance with its master production documents. Such certificates include a detailed summary of current batch documentation, with reference to respective dates of revision, manufacture, and packaging, and are signed and dated by the vendor’s quality control department. For drugs that are fabricated, packaged/labelled and tested in MRA countries, the batch certificate is considered to be equivalent. [Canadian GMP Guidelines 2009]
Certificate of Pharmaceutcial Product (CPP)
A certificate issued by the Inspectorate establishing the regulatory status of the pharmaceutical, biological, radiopharmaceutical or veterinary product listed and the GMP status of the fabricator of the product. This certificate is in the format recommended by the WHO. [Canadian GMP Guidelines 2009]
Certification of the Finished Product Batch
The certification in a register or equivalent document by a Qualified Person (QP), as defined in Article 51 of Directive 2001/83/EC and Article 55 of Directive 2001/82/EC, before a batch is released for sale or distribution. [EU GMP Guide, Annex 16]
Change Control
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure that the system is maintained in a validated state. [EU GMP Guide, Annex15, PIC/S PI 011-3]
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state. [Main Principles for Pharmaceutical Products, WHO, PIC/S PI 006-3]
A written procedure that describes the action to be taken if a change is proposed
(a) to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and testing of drugs, or
(b) that may affect the operation of the quality or support system.
[Canadian GMP Guidelines 2009]
Change Management
A systematic approach to proposing, evaluating, approving, implementing and reviewing changes. [ICH Q10]
A less formal approach to change control that is generally utilised during the preliminary planning and design stage of a project. (Many companies will elect to move straight to a change control system in a design stage of a complex project. This has the advantage of formality, more accurate records and documentation as well as a strong traceability and accountability feature). [PIC/S PI 006-3]
Changeover Procedure
(procédure de conversion) A logical series of validated steps that ensures the proper cleaning of suites and equipment before the processing of a different product begins. [Canadian GMP Guidelines 2009]
Chemical Development Studies
Studies conducted to scale-up, optimize, and validate the manufacturing process for a new drug substance. [ICH Q3A]
Chemical Transformation Step
For Chemical Entities, a step involved in the synthesis of the chemical structure of the drug substance from precursor molecular fragments. Typically it involves C-X or C-C bond formation or breaking. [ICH Q11]
Chiral
Not super imposable with its mirror image, as applied to molecules, conformations, and macroscopic objects, such as crystals. The term has been extended to samples of substances whose molecules are chiral, even if the macroscopic assembly of such molecules is racemic. [ICH Q6A]
Classical Fermentation
The term "classical fermentation" refers to processes that use microorganisms existing in nature and/or modified by conventional methods (e.g. irradiation or chemical mutagenesis) to produce APIs. APIs produced by "classical fermentation" are normally low molecular weight products such as antibiotics, amino acids, vitamins, and carbohydrates. [Chinese GMP Guidelines, Annex 2]
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. Note: The different degrees of environmental control are defined in the Supplementary Guidelines for the Manufacture of sterile medicinal products. [EU GMP Guide, Glossary]
An area (or room) 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. [Main Principles for Pharmaceutical Products, WHO]
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. [PIC/S PE 010-4]
An area with defined particle and microbiological cleanliness standards. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
(aire propre) A room or suite of rooms where Grade C or D conditions (see table in Section C.02.029 of these guidelines) are required. The rooms have a defined environmental control of particulate and microbial contamination and are constructed, maintained, and used in such a way as to minimize the introduction, generation, and retention of contaminants. [Canadian GMP Guidelines 2009]
Throughout this Ministerial Ordinance means the place, among those areas where the manufacturing operations are conducted (hereinafter referred to as “work areas”), where the weighing operations for the raw materials or the formulating operations for the drug substances are conducted or where the cleaned containers are exposed to the air in the work areas. [Japan MHLW Ministerial Ordinance No. 179, 2004]
Cleaning Validation
Cleaning validation is documented evidence that an approved cleaning procedure will provide equipment which is suitable for processing medicinal products. [EU GMP Guide, Annex 15]
Documented evidence to establish that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration factors such as batch size, dosing, toxicology and equipment size. [Main Principles for Pharmaceutical Products, WHO]
Documented evidence that an approved cleaning procedure will provide equipment which is suitable for processing of pharmaceutical products or active pharmaceutical ingredients (APIs). [PIC/S PI 006-3]
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Clinical Trial
Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s) and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of one or more investigational medicinal product(s) with the object of ascertaining its/their safety and/or efficacy. [EU GMP Guide, Annex 13]
Closed Isolator System
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Closed Procedure
A procedure whereby a sterile pharmaceutical product is prepared by transferring sterile ingredients or solutions to a pre-sterilised sealed container, either directly or using a sterile transfer device, without exposing the solution to the external environment. [PIC/S PE 010-4]
Closed System
Where a drug substance or product is not exposed to the immediate room environment during manufacture. [EU GMP Guide, Annex 2]
A system for collecting and/or processing blood in containers that have been connected together before sterilization, so that there is no possibility of microbial contamination from outside after collection of blood from the donor. [Canadian GMP Guidelines, Annex 14]
Cold Chain
(chaîne du froid) Maintenance of a designated temperature throughout the manufacturing process and during storage, until the product is used. [Canadian GMP Guidelines, Annex 2]
Colony Forming Units (CFU)
Visible outcome of growth of micro-organisms arising from a single or multiple cells. [PIC/S PI 012-3]
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Combination Product
A drug product which contains more than one drug substance [ICH Q6A]
Commercial Off-the-Shelf (COTS)
Configurable programs – stock programs that can be configured to specific user applications by “filling in the blanks”, without (COTS) altering the basic program. [PIC/S PI 011-3]
Commissioning
An engineering term that covers all aspects of bringing a system or sub-system to a position where it is regarded as being ready for use in pharmaceutical manufacture. Commissioning involves all the basis requirements of Installation Qualification (IQ) and Operational Qualification (OQ). [PIC/S PI 006-3]
The setting up, adjustment and testing of equipment or a system to ensure that it meets all the requirements, as specified in the user requirement specification, and capacities as specified by the designer or developer. Commissioning is carried out before qualification and validation. [TRS 961 Annex 7, WHO]
Commitment Batch
(lots de fabrication visés pour des essais systématiques) Production batches of a drug substance or drug product for which the stability studies are initiated or completed post approval through a commitment made in the registration application. [ICH Q1A, Canadian GMP Guidelines 2009]
Common Name
The international non-proprietary name recommended by the World Health Organization, or, if one does not exist, the usual common name. [Directive 2001/83/EC]
Comparability Bridging Study
A study performed to provide nonclinical or clinical data that allows extrapolation of the existing data from the drug product produced by the current process to the drug product from the changed process. [ICH Q5E]
Comparability Exercise
The activities, including study design, conduct of studies, and evaluation of data, that are designed to investigate whether the products are comparable. [ICH Q5E]
Comparable
A conclusion that products have highly similar quality attributes before and after manufacturing process changes and that no adverse impact on the safety or efficacy, including immunogenicity, of the drug product occurred. This conclusion can be based on an analysis of product quality attributes. In some cases, nonclinical or clinical data might contribute to the conclusion. [ICH Q5E]
Comparator Product
(médicament de comparaison) An investigational or marketed product (i.e. active control), or placebo, used as a reference in a clinical trial. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Complaint
Any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a [medical] device after it is released for distribution. [21 CFR Part 820, FDA]
Component
Any ingredient intended for use in the manufacture of a drug product, including those that may not appear in the final drug product.
[Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA, Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA, 21 CFR Part 210, FDA]
Any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled [medical] device. [21 CFR Part 820, FDA]
A unit of a drug, other than a radionuclide, separately packaged in a kit for use in the preparation of a radiopharmaceutical, or an empty vial or other accessory item in a kit. [Canadian GMP Guidelines 2009, Annex 3]
Compounding
A process wherein bulk drug substance is combined with another bulk drug substance and/or one or more excipients to produce a drug product. [PIC/S PI 007-6]
Compressed Gas
Gas which, when packaged under pressure for transport, is entirely gaseous at all temperatures above –50 °C. [EU GMP Guide, Annex 6]
Computer Hardware
Various pieces of equipment in the computer system, including the central processing unit, the printer, the modem, the cathode ray tube (CRT), and other related apparatus. [PIC/S PI 011-3]
Computer System
A group of hardware components and associated software, designed and assembled to perform a specific function or group of functions. [EU GMP Guide, Part II, ICH Q7]
Computer hardware components assembled to perform in conjunction with a set of software programs, which are collectively designed to perform a specific function or group of functions. [PIC/S PI 011-3]
Computerised System
A system including the input of data, electronic processing and the output of information to be used either for reporting or automatic control. [EU GMP Guide, Glossary]
A process or operation integrated with a computer system. [EU GMP Guide, Part II, ICH Q7]
A computer system plus the controlled function that it operates. [Authors note: Today this may be considered to be rather a narrow definition, especially in the context of integrated computers. The definition should therefore include all outside influences that interface with the computer system in its operating environment. These may typically include monitoring and network links, (to/from other systems or instruments), manual (keypad inputs), links to different media, manual procedures and automation. The term also covers automated instruments and systems. See also the definition for ‘automated systems’ in this section and Section 26, Reference 11, the GLP OECD consensus document. PIC/S GMP Annex 11(4) is relevant here regarding documenting the scope and interaction of systems.] [PIC/S PI 011-3]
Concurrent Production
(production simultanée) Simultaneous processing of more than one product in the same room/suite of a multi-product facility, or simultaneous processing of more than one lot of a product in a dedicated facility. [Canadian GMP Guidelines, Annex 2]
Concurrent Release
Releasing for distribution a lot of finished product, manufactured following a qualification protocol, that meets the lot release criteria established in the protocol, but before the entire study protocol has been executed [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Concurrent Validation
Validation carried out in exceptional circumstances, justified on the basis of significant patient benefit, where the validation protocol is executed concurrently with commercialisation of the validation batches. [EU GMP Guide, Annex 15]
Validation carried out during routine production of products intended for sale. [PIC/S PI 006-3]
Confidential Unit Exclusion (CUE)
A system that allows the donor, in private, to indicate that his/her collected blood should, or should not, be used for transfusion to another individual.
[Canadian GMP Guide, Annex 14]
Configuration
The documented physical and functional characteristics of a particular item, or system, e.g. software, computerised system, hardware, firmware and operating system. A change converts one configuration into a new one. [PIC/S PI 011-3]
Configuration Management
The process of identifying and defining the configuration items in a system, controlling the release and change of these items throughout the system life cycle, recording and reporting the status of configuration items and change requests, and verifying the completeness and correctness of configuration items. [PIC/S PI 011-3]
Confirmation
A signed statement that a process or test has been conducted in accordance with GMP and the relevant marketing authorisation, as agreed in writing with the Qualified Person responsible for certifying the finished product batch before release. Confirm and confirmed have equivalent meanings.
[EU GMP Guide, Annex 16]
Confirmatory Studies
Studies undertaken to establish photostability characteristics under standardized conditions. These studies are used to identify precautionary measures needed in manufacturing or formulation and whether light resistant packaging and/or special labeling is needed to mitigate exposure to light. For the confirmatory studies, the batch(es) should be selected according to batch selection for long-term and accelerated testings which is described in the Parent Guideline. [ICH Q1B]
Conjugated Product
A conjugated product is made up of an active ingredient (for example, peptide, carbohydrate) bound covalently or noncovalently to a carrier (for example, protein, peptide, inorganic mineral) with the objective of improving the efficacy or stability of the product. [ICH Q5C]
Consignment
The quantity of a pharmaceutical(s), made by one manufacturer and supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include material belonging to more than one batch. [Main Principles for Pharmaceutical Products, WHO]
The quantity of pharmaceutical products supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include pharmaceutical products belonging to more than one batch. [Good Distribution Practices for Pharmaceutical Products, WHO]
The quantity of a bulk starting material, or of a drug product, made by one manufacturer or supplied by an agent, and supplied at one time in response to a particular request or order. A consignment may comprise one or more lot-identified packages or containers and may include material belonging to more than one lot-identified batch. [Sampling Operations, WHO]
Constituent with Known Therapeutic Activity
Substances or groups of substances which are chemically defined and known to contribute to the therapeutic activity of a herbal material or of a preparation. [Good Manufacturing Practices: Specific Pharmaceutical Products, WHO]
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. [EU GMP Guide, Glossary]
Container
A container is a cryogenic vessel (tank, tanker or other type of mobile cryogenic vessel) a cylinder, a cylinder bundle or any other package that is in direct contact with the gas. [EU GMP Guide, Annex 6]
The material employed in the packaging of a pharmaceutical product. Containers include primary, secondary and transportation containers. Containers are referred to as primary if they are intended to be in direct contact with the product. Secondary containers are not intended to be in direct contact with the product. [Good Distribution Practices for Pharmaceutical Products, WHO]
Container Closure System
The sum of packaging components that together contain and protect the dosage form. This includes primary packaging components and secondary packaging components, if the latter are intended to provide additional protection to the drug product. A packaging system is equivalent to a container closure system. [ICH Q1A]
Containment
The action of confining a biological agent or other entity within a defined space. [EU GMP Guide, Glossary]
A process or device to contain product, dust or contaminants in one zone, preventing it from escaping to another zone. [TRS 957 Annex 5, WHO]
(confinement) Total isolation of one or more steps of a manufacturing process to prevent cross-contamination of the product, or staff, from all other steps of the process. [Canadian GMP Guidelines 2009, Annex 2]
(primary)
EA 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. [EU GMP Guide, Glossary]
(secondary)
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 sterilisers for the exit of materials and secure operating procedures. In many cases it may add to the effectiveness of primary containment. [EU GMP Guide, Glossary]
Contaminant
Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not intended to be part of the manufacturing process of the drug substance or drug product. [ICH Q6B]
Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, inter mediate, or API during production, sampling, packaging or repackaging, storage or transport. [EU GMP Guide, Part II, ICH Q7]
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a starting material, or intermediate or finished product during production, sampling, packaging or repackaging, storage or transport. [Guide to good storage practices for pharmaceuticals, WHO]
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, in-process material, or phase 1 investigational drug during manufacturing, sampling, packaging or repackaging, storage, or transport. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Continous Cell Line
A cell line having an infinite capacity for growth. Often referred to as "“immortal”" and previously referred to as “established”. [ICH Q5D]
Continous Culture
(culture en continu) Process by which growth of cells is maintained by periodically replacing a portion of the cells and medium such that there is no lag or saturation phase. [Canadian GMP Guidelines, Annex 2]
Continous Process Verification
An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. [ICH Q8]
Continual Improvement
Recurring activity to increase the ability to fulfil requirements. (ISO 9000:2005). [ICH Q10]
Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Contract Facility
Organisation performing work associated with the manufacturing process for the manufacturer. [Canadian GMP Guide, Annex 14]
Contract Manufacturer
A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer. [EU GMP Guide, Part II, ICH Q7]
Control Measure
Any action and activity that can be used to prevent or eliminate a pharmaceutical quality hazard or reduce it to an acceptable level. [Hazard and Risk Analysis, WHO]
Control Number
see Batch Number
Control Strategy
A planned set of controls, derived from current product and process understanding, that assures process performance and product quality. The controls can include
parameters and attribtues related to drug substance and drug product materials and components,
facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. [ICH Q10]
Controlled Area
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 negative to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. [EU GMP Guide, Glossary]
Controlled Work Area
An enclosed work area constructed and operated in such a manner and equipped with appropriate air handling and filtration systems to reduce to a pre-defined level the introduction, generation and retention of contaminants. A controlled work area may also be used to protect the external environment from the materials being handled in it e.g. vaccines or cytotoxics. [PIC/S PE 010-4]
Correction
Repair, rework, or adjustment relating to the disposition of an existing discrepancy. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Action to eliminate a detected non-conformity. Note 1: There is a distinction between correction and corrective action. A correction can be made in conjunction with a corrective action. Note 2: A correction can be, for example, rework or reclassification. [ISO 9000:2005]
Corrective Action (CA)
Action to eliminate the cause of a detected non-conformity or other undesirable situation. NOTE: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the causes of an existing discrepancy or other undesirable situation to prevent recurrence. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Corrective Action and Preventive Action
see CAPA
COTS
see Commercial Off-the-Shelf
Counterfeit Pharmaceutical Product
A pharmaceutical product which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products, and counterfeit pharmaceutical products may include products with the correct ingredients, with the wrong ingredients, without active ingredients, with an incorrect quantity of active ingredient or with fake packaging. [Good Distribution Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Critical
Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification. [EU GMP Guide, Part II, ICH Q7]
Critical Area / Critical Zone
That part of the controlled work area where containers are opened and the product is exposed. Particulate and microbiological contamination should be reduced to levels appropriate to the intended use. [PIC/S PE 010-4]
Zone within the Aseptic Processing Area where sterile product, product components or product contact surfaces are exposed to the environment. [PIC/S PE 014-4]
An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas. [FDA Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – cGMP]
Area in which the sterilized drug product, containers, and closures are exposed to environmental conditions that must be designed to maintain product sterility. Activities conducted in this area include manipulations, such as aseptic connections, sterile ingredient additions, filling and closing operations. [Canadian GMP Guidelines 2009]
Critical Control Point(CCP)
A step at which control can be applied and is essential to prevent or eliminate a pharmaceutical quality hazard or to reduce it to an acceptable level. [TRS 961 Annex 7, WHO]
Critical Labelling
Labelling which identifies a product or status, such as a quarantine label or blood group label, if it is used to control release for inventory. [Canadian GMP Guidelines, Annex 14]
Critical Operation
An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical product. [Main Principles for Pharmaceutical Products, WHO]
Critical Process Parameter (CPP)
A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. [ICH Q8]
Critical Quality Attribute (CQA)
A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. [ICH Q8]
This refers to attributes of physical, chemical, biological or microorganism, should be of certain limits, scope or distribution, so as to meet expectant product quality. [Chinese GMP Guidelines, Annex 2]
Critical Surface
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. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Critical Variable Study
A study that serves to measure variables (parameters) critical to the satisfactory operation of a piece of equipment or plant and to assure their operation within monitored and controlled limits. Examples of variables would be pressure, temperature, flow rates, time etc. [PIC/S PI 006-3]
Cross-Contamination
Contamination of a material or of a product with another material or product. [EU GMP Guide Part I, Glossary, ICH Q7, PIC/S PE 010-4]
Contamination of a starting material, intermediate product or finished product with another starting material or product during production. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Contamination of a material or phase 1 investigational drug with another material or product. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Contamination of a drug or biological starting material or in-process intermediate with another drug or biological starting material or in-process intermediate. In multi-product facilities, cross-contamination can occur throughout the manufacturing process, from generation of the MCB and WCB through finishing. [Canadian GMP Guidelines 2009, Annex 2]
Crude Plant/Vegetable Drug
Fresh or dried medicinal plant or parts thereof. [EU GMP Guide, Glossary]
Customer
A person or organization (internal or external) that receives a product or service anywhere along the product’s life cycle.
[Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Cylinder
A container designed to contain gas at a high pressure. [EU GMP Guide, Glossary]
Container usually cylindrical suited for compressed, liquefied or dissolved gas, fitted with a device to regulate the spontaneous outflow of gas at atmospheric pressure and room temperature. [EU GMP Guide, Annex 6]
Cylinder Bundle
An assembly of cylinders that are fastened together, interconnected by a manifold and transported and used as a unit. [EU GMP Guide, Annex 6]
Cyrogenic Gas
A gas which liquefies at 1.013 bar at temperatures below -150 °C. [EU GMP Guide, Annex 6]
Cyrogenic Vessel
A container designed to contain liquefied gas at extremely low temperature. [EU GMP Guide, Glossary]