Useful Terms and Definition for pharmaceutical based on MHRA
What is Acceptance criteria?
Numerical limits, ranges, or other suitable measures for acceptance of test results.
What is Active Pharmaceutical Ingredient (API) (or drug substance)?
Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
What is Active substance gas?
Any gas intended to be an active substance for a medicinal product.
What is Active substance?
See Article 1(3a) of Directive 2001/83/EC.
What is Adjuvant?
A chemical or biological substance that enhances the immune response against an antigen.
What is Antigens?
Substances (e.g. toxins, foreign proteins, bacteria, tissue cells) capable of inducing specific immune responses.
What is Antibody?
Proteins produced by the B-lymphocytes that bind to specific antigens. Antibodies may divided into two main types based on key differences in their method of manufacture: Monoclonal antibodies (MAb) – homogenous antibody population obtained from a single clone of lymphocytes or by recombinant technology and which bind to a single epitope. Polyclonal antibodies – derived from a range of lymphocyte clones, produced in human and animals in response to the epitopes on most ‘non-self’ molecules.
What is Air-lock?
An enclosed space with two or more doors, and which is interposed between two or more rooms, e.g. of differing class of cleanliness, for the purpose of controlling the air-flow between those rooms when they need to be entered. An air-lock is designed for and used by either people or goods.
What is Air separation?
Separation of atmospheric air into its constituent gases using fractional distillation at cryogenic temperatures.
What is Allergoids?
Allergens which are chemically modified to reduce IgE reactivity.
What is Application?
Software installed on a defined platform/hardware providing specific functionality.
What is API starting material?
A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials are normally of defined chemical properties and structure.
What is Area?
A specific set of rooms within a building associated with the manufacturing of any one product or multiple products that has a common air handling unit.
What is Batch (or lot)?
A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continuous production, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount produced in a fixed time interval.
A defined quantity of starting material, packaging material or product processed in one process or series of processes so that it could be expected to be homogeneous. Note: To complete certain stages of manufacture, it may be necessary to divide a batch into a number of sub-batches, which are later brought together to form a final homogeneous batch. In the case of continuous manufacture, the batch must correspond to a defined fraction of the production, characterised by its intended homogeneity For control of the finished product, the following definition has been given in Annex 1 of Directive 2001/83/EC as amended by Directive 2003/63/EC “For the control of the finished product, a batch of a proprietary medicinal product comprises all the units of a pharmaceutical form which are made from the same initial mass of material and have undergone a single series of manufacturing operations or a single sterilisation operation or, in the case of a continuous production process, all the units manufactured in a given period of time.”
What is Batch number (or lot number)?
A unique combination of numbers, letters and/or symbols that identifies a batch (or lot) and from which the production and distribution history can be determined. A distinctive combination of numbers and/or letters which specifically identifies a batch.
What is Bespoke/ customized computerised system?
A computerised system individually designed to suit a specific business process.
What is Bioburden?
The level and type (e.g. objectionable or not) of micro-organisms that can be present in raw materials, API starting materials, intermediates or APIs. Bioburden should not be considered contamination unless the levels have been exceeded or defined objectionable organisms have been detected. The level and type (i.e. objectionable or not) of micro-organism present in raw materials, media, biological substances, intermediates or products. Regarded as contamination when the level and/or type exceed specifications.
What is Biogenerator?
A contained system, such as a fermenter, into which biological agents are introduced along with other materials so as to effect their multiplication or their 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.
What is Biological agents?
Micro-organisms, including genetically engineered micro-organisms, cell cultures and endoparasites, whether pathogenic or not.
What is Biological medicinal product
See 3rd paragraph of point 3.2.1.1.b. of Part I of Annex I to Directive 2001/83/EC.
What is Biosafety level (bsl)?
The containment conditions required to safely handle organisms of different hazards ranging from BSL1 (lowest risk, unlikely to cause human disease) to BSL4 (highest risk, cause severe disease, likely to spread and no effective prophylaxis or treatment available).
What is Blood?
Blood, as referred to in Directive 2002/98/EC (Art. 3a), means whole blood collected from a donor and processed either for transfusion or for further manufacturing.
What is Blood component?
A blood component, as referred to in Directive 2002/98/EC (Art. 3b), means a therapeutic constituent of blood (red cells, white cells, platelets and plasma) that can be prepared by various methods.
What is Blood establishment?
A blood establishment, as referred to in Directive 2002/98/EC (Art. 3e), is any structure or body that is responsible for any aspect of the collection and testing of human blood and blood components, whatever their intended purpose, and their processing, storage and distribution when intended for transfusion. While this definition does not include hospital blood banks, it is understood to include centres where apheresis of plasma is performed.
Blood products?
A blood product, as referred to in Directive 2002/98/EC (Art. 3c), means any therapeutic product derived from human blood or plasma.
Blinding?
A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). In relation to an investigational medicinal product, blinding shall mean the deliberate disguising of the identity of the product in accordance with the instructions of the sponsor. Unblinding shall mean the disclosure of the identity of blinded products.
What is Brokering of active substances?
All activities in relation to the sale or purchase of active substances that do not include physical handling and that consist of negotiating independently and on behalf of another legal or natural person.
What is Bracketing approach?
A science and risk based validation approach such that only batches on the extremes of certain predetermined and justified design factors, e.g. strength, batch size and/or pack size, are tested during process validation. The design assumes that validation of any intermediate levels is represented by validation of the extremes. Where a range of strengths is to be validated, bracketing could be applicable if the strengths are identical or very closely related in composition, e.g. for a tablet range made with different compression weights of a similar basic granulation or a capsule range made by filling different plug fill weights of the same basic composition into different size capsule shells. Bracketing can be applied to different container sizes or different fills in the same container closure system.
What is Bulk product?
Any product which has completed all processing stages up to, but not including, final packaging.
What is Calibration?
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. 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.
What is 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.
What is 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. 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.
What is Cell culture?
The result from the in-vitro growth of cells isolated from multicellular organisms.
What is 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.
What is Change control?
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action to ensure and document that the system is maintained in a validated state.
What is 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.
What is 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 area at the same time.
What is Cleaning validation?
Cleaning validation is documented evidence that an approved cleaning procedure will reproducibly remove the previous product or cleaning agents used in the equipment below the scientifically set maximum allowable carryover level.
What is Cleaning verification?
The gathering of evidence through chemical analysis after each batch/ campaign to show that the residues of the previous product or cleaning agents have been reduced below the scientifically set maximum allowable carryover level.
What is 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.
What is Closed system?
Where a drug substance or product is not exposed to the immediate room environment during manufacture.
What is Comparator product?
An investigational or marketed product (i.e. active control), or placebo, used as a reference in a clinical trial.
What is Commercial off the shelf software?
Software commercially available, whose fitness for use is demonstrated by a broad spectrum of users.
What is Compressed gas?
Gas which, when packaged under pressure for transport, is entirely gaseous at all temperatures above 50˚C.
What is 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 sterilisers for the exit of materials and secure operating procedures. In many cases it may add to the effectiveness of primary containment.
What is 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.
What is Contained use?
See Article 2(c) of Directive 2009/41/EC for all genetically modified organisms.
What is 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.
What is 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.
What is 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.
What is Continuous process verification?
An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (ICH Q8)
What is Control strategy?
A planned set of controls derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes 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)
What is Computer system?
A group of hardware components and associated software, designed and assembled to perform a specific function or group of functions. A system including the input of data, electronic processing and the output of information to be used either for reporting or automatic control.
What is Computerized system?
A process or operation integrated with a computer system.
What is Consignee?
The person to whom the shipment is to be delivered whether by land, sea or air.
What is Contamination?
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or active substance during production, sampling, packaging or repackaging, storage or transport.
What is Contract manufacturer?
A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer.
What is 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.
What is 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)
What is Critical quality attribute (cqa)?
A physical, chemical, biological or microbiological property or characteristic that should be within an approved limit, range or distribution to ensure the desired product quality. (ICH Q8)
What is Cross-contamination?
Contamination of a material or product with another material or product.
What is Crude plant (vegetable drug)?
Fresh or dried medicinal plant or parts thereof.
What is Cryogenic vessel?
A container designed to contain liquefied gas at extremely low temperature.
What is Cryogenic gas?
A gas which liquefies at 1.013 bar at temperatures below 150˚C.
What is Cylinder?
A container designed to contain gas at a high pressure. 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.
What is Cylinder bundle?
An assembly of cylinders that are fastened together, interconnected by a manifold and transported and used as a unit.
What is Design qualification (dq)?
The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.
What is Design space?
The multidimensional combination and interaction of input variables, e.g. material attributes, and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (ICH Q8)
What is Deliberate release?
See Article 2(3) of Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC.34
What is Distribution of active substances?
All activities consisting of procuring, importing, holding, supplying or exporting of active substances, apart from brokering.
What is Deviation?
Departure from an approved instruction or established standard.
What is Drug (medicinal) product?
The dosage form in the final immediate packaging intended for marketing. (Reference Q1A).
What is Drug substance?
See Active Pharmaceutical Ingredient
What is Expiry date?
The date placed on the container/labels of an active substance designating the time during which the active substance is expected to remain within established shelf life specifications if stored under defined conditions, and after which it should not be used.
What is Evacuate?
To remove the residual gas from a container / system to a pressure less than 1.013 bar, using a vacuum system.
What is Exotic organism?
A biological agent where either the corresponding disease does not exist in a given country or geographical area, or where the disease is the subject of prophylactic measures or an eradication programme undertaken in the given country or geographical area.
What is Excipient?
See Article 1(3b) of Directive 2001/83/EC.
What is Ex-vivo?
Where procedures are conducted on tissues or cells outside the living body and returned to the living body.
What is Falsified active substance?
Any active substance with a false representation of: (a) its identity, including its packaging and labelling, its name or its components as regards any of the ingredients and the strength of those ingredients; (b) its source, including its manufacturer, its country of manufacture, its country of origin; or (c) its history, including the records and documents relating to the distribution channels used.
What is Feeder cells?
Cells used in co-culture to maintain pluripotent stem cells. For human embryonic stem cell culture, typical feeder layers include mouse embryonic fibroblasts (MEFs) or human embryonic fibroblasts that have been treated to prevent them from dividing.
What is Finished product?
A medicinal product which has undergone all stages of production, including packaging in its final container.
What is Fractionation, fractionation plant?
Fractionation is the manufacturing process in a plant (fractionation plant) during which plasma components are separated/purified by various physical and chemical methods such as e.g. precipitation, chromatography.
What is Gas?
Any substance that is completely gaseous at 1.013 bar and +20˚C or has a vapour pressure exceeding 3 bar at +50˚C.
What is Gene?
A sequence of DNA that codes for one (or more) protein(s).
What is Gene transfer?
A process to transfer a gene in cells, involving an expression system contained in a delivery system known as a vector, which can be of viral, as well as non-viral origin. After gene transfer, genetically modified cells are also termed transduced cells.
What is Genetically modified organism (gmo)?
See Article 2(2) of Directive 2001/18/EC.
What is Good practice guidelines?
Good practice guidelines give interpretation on the Community standards and specifications defined for quality systems in blood establishments established in the Annex of Directive 2005/62/EC.1
What is Home cryogenic vessel?
Mobile cryogenic vessel designed to hold liquid oxygen and dispense gaseous oxygen at patients’ home.
What is Hapten?
A low molecular weight molecule that is not in itself antigenic unless conjugated to a “carrier” molecule.
What is Hybridoma?
An immortalised cell line that secrete desired (monoclonal) antibodies and are typically derived by fusing B-lymphocytes with tumour cells.
What is Holding?
Storing active substances.
What is Hot–cells?
Shielded workstations for manufacture and handling of radioactive materials. Hot-cells are not necessarily designed as an isolator.
What is Herbal medicinal product?
Medicinal product containing, as active ingredients, exclusively plant material and/or vegetable drug preparations.
What is Hydrostatic pressure test?
Test performed as required by national or international regulations, in order to ensure that pressure containers are able to withstand pressures up to the container’s design pressure.
What is Impurity?
Any component present in the intermediate or API that is not the desired entity.
What is Impurity profile?
A description of the identified and unidentified impurities present in an API.
What is Infected?
Contaminated with extraneous biological agents and therefore capable of spreading infection.
What is In-process control (or process control)?
Checks performed during production in order to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or API conforms to its specifications. Checks performed during production in order to monitor and if necessary to adjust the process to ensure that the product conforms its specification. The control of the environment or equipment may also be regarded as a part of in-process control.
What is Installation qualification (iq)?
The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations.
What is Intermediate?
A material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (Note: this Guide only addresses those intermediates produced after the point that the company has defined as the point at which the production of the API begins.) Partly processed material which must undergo further manufacturing steps before it becomes a bulk product.
What is Intermediate product?
See definitions in GMP Glossary and in Part II.
What is Investigational medicinal product?
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorisation when used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form.
What is Investigator?
A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.
What is In-vivo?
Procedures conducted in living organisms.
What is It infrastructure?
The hardware and software such as networking software and operation systems, which makes it possible for the application to function.
What is Knowledge management?
A systematic approach to acquire, analyse, store and disseminate information. (ICH Q10)
What is Lifecycle?
All phases in the life of a product, equipment or facility from initial development or use through to discontinuation of use. All phases in the life of the system from initial requirements until retirement including design, specification, programming, testing, installation, operation, and maintenance.
What is Liquifiable gases?
Those which, at the normal filling temperature and pressure, remain as a liquid in the cylinder.
What is Liquefied gas?
A gas which, when packaged for transport, is partially liquid (or solid) at a temperature above 50˚C.
What is Lot?
See Batch
What is Lot number?
See Batch Number
What is Look-back?
Documented procedure to trace biological medicinal substances or products which may be adversely affected by the use or incorporation of animal or human materials when either such materials fail release tests due to the presence of contaminating agent(s) or when conditions of concern become apparent in the source animal or human.
What is Manufacture?
All operations of receipt of materials, production, packaging, repackaging, labelling, relabelling, quality control, release, storage, and distribution of APIs and related controls.
What is Manufacturing?
Production, quality control and release and delivery of radiopharmaceuticals from the active substance and starting materials.
What is Material?
A general term used to denote raw materials (starting materials, reagents, solvents), process aids, intermediates, APIs and packaging and labelling materials.
What is Manifold?
Equipment or apparatus designed to enable one or more gas containers to be filled simultaneously from the same source. Equipment or apparatus designed to enable one or more gas containers to be emptied and filled at the same time.
What is Manufacturer/importer of investigational medicinal products?
Any person engaged in activities for which the authorisation referred to in Article 13(1) of Directive 2001/20/EC is required.
What is Master cell bank (mcb)?
An aliquot of a single pool of cells which generally has been prepared from the selected cell clone under defined conditions, dispensed into multiple containers and stored under defined conditions. The MCB is used to derive all working cell banks. Master virus seed (MVS) – as above, but in relation to viruses; master transgenic bank – as above but for transgenic plants or animals.
What is Maximum theoretical residual impurity?
Gaseous impurity from a possible backflow that remains after the cylinder pre-treatment process before filling. The calculation of the maximum theoretical residual impurity is only relevant for compressed gases and assumes that the gases behave as perfect gases.
What is Medicinal products derived from human blood or human plasma?
Medicinal products derived from human blood or human plasma, as referred to in Directive 2001/83/EC (Art. 1 No. 10), are medicinal products based on blood constituents which are prepared industrially by public or private establishments.
What is Medicinal gas?
Any gas or mixture of gases classified as a medicinal product (as defined in Directives 2001/83/EC and 2001/82/EC).
What is Medicinal plant?
Plant the whole or part of which is used for medicinal purpose.
What is Medicinal product?
Any substance or combination of substances presented for treating or preventing disease in human beings or animals. Any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in human beings or in animals is likewise considered a medicinal product.
What is Minimum pressure retention valve?
A cylinder valve, which maintains a positive pressure above atmospheric pressure in a gas cylinder after use, in order to prevent internal contamination of the cylinder.
What is Mother liquor?
The residual liquid which remains after the crystallization or isolation processes. A mother liquor may contain unreacted materials, intermediates, levels of the API and/or impurities. It may be used for further processing.
What is Mobile cryogenic vessel?
Mobile thermally insulated container designed to maintain the contents in a liquid state. In the Annex, this term does not include the tankers.
What is Monosepsis (axenic)?
A single organism in culture which is not contaminated with any other organism.
What is Multi-product facility?
A facility that manufactures, either concurrently or in campaign mode, a range of different biological medicinal substances and products and within which equipment train(s) may or may not be dedicated to specific substances or products.
What is Non-return valve?
Valve, which permits flow in one direction only.
What is Ongoing process verification (also known as continued process
Verification)?
Documented evidence that the process remains in a state of control during commercial manufacture.
What is Order?
Instruction to process, package and/or ship a certain number of units of investigational medicinal product(s).
What is Operational qualification (oq)?
The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.
What is Packaging material?
Any material intended to protect an intermediate or API during storage and transport. Any material employed in the packaging of a medicinal 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.
What is Packaging?
All operations, including filling and labelling, which a bulk product has to undergo in order to become a finished product. Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being the filled, but not finally packaged, primary containers.
What is Packaging material?
Any material employed in the packaging of a medicinal 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.
What is Performance qualification (pq)?
The documented verification that systems and equipment can perform effectively and reproducibly based on the approved process method and product specification.
What is Plasma for fractionation?
Plasma for fractionation is the liquid part of human blood remaining after separation of the cellular elements from blood collected in a container containing an anticoagulant, or separated by continuous filtration or centrifugation of anti-coagulated blood in an apheresis procedure; it is intended for the manufacture of plasma derived medicinal products, in particular albumin, coagulation factors and immunoglobulins of human origin and specified in the European Pharmacopoeia (Ph. Eur.) monograph “Human Plasma for fractionation” (0853).
What is Plasma master file (pmf)?
A Plasma Master File, as referred to in Directive 2001/83/EC (Annex I, Part III, No. 1.1.a), is a stand-alone document, which is separate from the dossier for marketing authorisation. It provides all relevant detailed information on the characteristics of the entire human plasma used as a starting material and/or a raw material for the manufacture of sub/ intermediate fractions, constituents of the excipients and active substances, which are part of plasma, derived medicinal products or medical devices.
What is Plasmid?
A plasmid is a piece of DNA usually present in a bacterial cell as a circular entity separated from the cell chromosome; it can be modified by molecular biology techniques, purified out of the bacterial cell and used to transfer its DNA to another cell.
What is Preparation?
Handling and radiolabelling of kits with radionuclide eluted from generators or radioactive precursors within a hospital. Kits, generators and precursors should have a marketing authorisation or a national licence.
What is Processing?
According to the terminology of Directive 2005/62/EC, “processing means any step in the preparation of blood component that is carried out between the collection of blood and the issuing of a blood component”, e.g. separation and freezing of blood components. In this Annex, processing in addition refers to those operations performed at the blood establishment that are specific to plasma to be used for fractionation.
What is Procedure?
A documented description of the operations to be performed, the precautions to be taken and measures to be applied directly or indirectly related to the distribution of an active substance. 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.
What is Process aids?
Materials, excluding solvents, used as an aid in the manufacture of an intermediate or API that do not themselves participate in a chemical or biological reaction (e.g. filter aid, activated carbon, etc).
What is Process control?
See In-Process Control.
What is Process owner?
The person responsible for the business process.
What is Production?
All operations involved in the preparation of an API from receipt of materials through processing and packaging of the API. All operations involved in the preparation of a medicinal product, from receipt of materials, through processing and packaging, to its completion as a finished product.
What is Product realisation?
Achievement of a product with the quality attributes to meet the needs of patients, health care professionals and regulatory authorities and internal customer requirements. (ICH Q10)
What is Product specification file?
A reference file containing, or referring to files containing, all the information necessary to draft the detailed written instructions on processing, packaging, quality control testing, batch release and shipping of an investigational medicinal product.
What is Procuring?
Obtaining, acquiring, purchasing or buying active substances from manufacturers, importers or other distributors.
What is Process validation?
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.
What is Prospective validation?
Validation carried out before routine production of products intended for sale.
What is Purge?
To remove the residual gas from a container / system by first pressurising and then venting the gas used for purging to 1.013 bar.
What is Quality by design?
A systematic approach that begins with predefined objectives and emphasises product and process understanding and process control, based on sound science and quality risk management.
What is Qualification?
Action of proving and documenting that equipment or ancillary systems are properly installed, work correctly, and actually lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation. Action of proving that any equipment works correctly and actually leads to the expected results. The word validation is sometimes widened to incorporate the concept of qualification.
What is Quality Assurance (QA)?
The sum total of the organised arrangements made with the object of ensuring that all APIs are of the quality required for their intended use and that quality systems are maintained.
What is Quality control (qc)?
Checking or testing that specifications are met.
What is Quality unit(s)?
An organizational unit independent of production which fulfills both Quality Assurance and Quality Control responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization.
What is Quality risk management?
A systematic process for the assessment, control, communication and review of risks to the quality of an active substance across the product lifecycle. A systematic process for the assessment, control, communication and review of risks to quality across the lifecycle. (ICH Q9)
What is Quality system?
The sum of all aspects of a system that implements quality policy and ensures that quality objectives are met (ICH Q9).
What is Qualified person (qp)?
The qualified person is the person referred to in Directive 2001/83/EC (Art. 48). QP as described in Directives 2001/83/EC and 2001/82/EC. QP responsibilities are elaborated in Eudralex Volume 4, annex 16.
What is Quarantine?
The status of materials isolated physically or by other effective means pending a decision on the subsequent approval or rejection. The status of starting or packaging materials, intermediate, bulk or finished products isolated physically or by other effective means whilst awaiting a decision on their release or refusal.
What is Randomisation
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.
What is Randomisation code?
A listing in which the treatment assigned to each subject from the randomisation process is identified.
What is Raw material?
A general term used to denote starting materials, reagents, and solvents intended for use in the production of intermediates or APIs. See 4th paragraph of point 3.2.1.1.b. of Part I of Annex I to Directive 2001/83/EC.
What is Radiopharmaceutical?
“Radiopharmaceutical” shall mean any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose (Article 1(6) of Directive 2001/83/EC).
What is Reconciliation?
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically and actually produced or used.
What is Record?
See GMP Guide, Chapter 4.
What is Recovery?
The introduction of all or part of previous batches of the required quality into another batch at a defined stage of manufacture.
What is Reprocessing?
The reworking of all or part of a batch of product of an unacceptable quality from a defined stage of production so that its quality may be rendered acceptable by one or more additional operations.
What is Responsible person (rp)?
The responsible person is the person referred to in Directive 2002/98/EC (Art. 9). The person designated in accordance with Article 17 of Directive 2004/23/EC.
What is Return?
Sending back to the manufacturer or distributor of a medicinal product which may or may not present a quality defect.
What is Reference standard, primary?
A substance that has been shown by an extensive set of analytical tests to be authentic material that should be of high purity. This standard can be: (1) obtained from an officially recognised source, or (2) prepared by independent synthesis, or (3) obtained from existing production material of high purity, or (4) prepared by further purification of existing production material.
What is Reference standard, secondary?
A substance of established quality and purity, as shown by comparison to a primary reference standard, used as a reference standard for routine laboratory analysis.
What is Reprocessing?
Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the established manufacturing process. Continuation of a process step after an in-process control test has shown that the step is incomplete is considered to be part of the normal process, and not reprocessing.
What is Retest date?
The date when a material should be re-examined to ensure that it is still suitable for use.
What is Reworking?
Subjecting an intermediate or API that does not conform to standards or specifications to one or more processing steps that are different from the established manufacturing process to obtain acceptable quality intermediate or API (e.g., recrystallizing with a different solvent).
What is Scaffold?
A support, delivery vehicle or matrix that may provided structure for or facilitate the migration, binding or transport of cells and/or bioactive molecules.
What is Seed lot?
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˚C. A freeze-dried master seed lot is stored at a temperature known to ensure stability. Working seed lot: A culture of a micro-organism derived 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.
What is Shipping?
The operation of packaging for shipment and sending of ordered medicinal products for clinical trials.
What is Signed (signature)?
The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature.
What is Signature (signed)?
See definition for signed
What is Simulated agents?
A material that closely approximates the physical and, where practical, the chemical characteristics, e.g. viscosity, particle size, pH etc., of the product under validation.
What is Solvent?
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API.
What is Somatic cells?
Cells, other than reproductive (germ line) cells, which make up the body of a human or animal. These cells may be autologous (from the patient), allogeneic (from another human being) or xenogeneic (from animals) somatic living cells, that have been manipulated or altered ex vivo, to be administered in humans to obtain a therapeutic, diagnostic or preventive effects.
What is Specification?
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. “Conformance to specification” means that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria.
What is Specified pathogen free (spf)?
Animal materials (e.g. chickens, embryos or cell cultures) used for the production or quality control of biological medicinal products derived from groups (e.g. flocks or herds) of animals free from specified pathogens. Such flocks or herds are defined as animals sharing a common environment and having their own caretakers who have no contact with non-SPF groups.
What is Sponsor?
An individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial.
What is State of control?
A condition in which the set of controls consistently provides assurance of acceptable process performance and product quality
What is Starting material?
Any substance used in the production of a medicinal product, but excluding packaging materials. See the 1st and 2nd paragraph of point 3.2.1.1.b of Part I of Annex I to Directive 2001/83/EC.
What is Sterility?
Sterility is the absence of living organisms. The conditions of the sterility test are given in the European Pharmacopoeia.
What is Supplying?
All activities of providing, selling, donating active substances to distributors, pharmacists, or manufacturers of medicinal products.
What is System?
Is used in the sense of a regulated pattern of interacting activities and techniques which are united to form an organised whole.
What is System owner?
The person responsible for the availability, and maintenance of a computerised system and for the security of the data residing on that system.
What is Tank?
Static thermally insulated container designed for the storage of liquefied or cryogenic gas. They are also called “Fixed cryogenic vessels”.
What is Tanker?
In the context of the Annex, thermally insulated container fixed on a vehicle for the transport of liquefied or cryogenic gas.
What is Traditional approach?
A product development approach where set points and operating ranges for process parameters are defined to ensure reproducibility.
What is Transgenic?
An organism that contains a foreign gene in its normal genetic component for the expression of biological pharmaceutical materials.
What is Third countries contract fractionation program?
This is a contract fractionation in a plant of a fractionator/manufacturer in the EU/EEA, using starting material from third countries and manufacturing products not intended for the EU/EEA market.
What is Transport (transportation)?
Moving active substances between two locations without storing them for unjustified periods of time.
What is Third party?
Parties not directly managed by the holder of the manufacturing and/or import authorisation.
What is User requirements specification (urs)?
The set of owner, user and engineering requirements necessary and sufficient to create a feasible design meeting the intended purpose of the system.
What is Validation?
A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria. Action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity or system actually leads to the expected results (see also qualification).
What is Validation protocol?
A written plan stating how validation will be conducted and defining acceptance criteria. For example, the protocol for a manufacturing process identifies processing equipment, critical process parameters/operating ranges, product characteristics, sampling, test data to be collected, number of validation runs, and acceptable test results.
What is Valve?
Device for opening and closing containers.
What is Vent?
To remove the residual gas from a container / system down to 1.013 bar, by opening the container / system to atmosphere.
What is Vector?
An agent of transmission, which transmits genetic information from one cell or organism to another, e.g. plasmids, liposomes, viruses.
What is Viral vector?
A vector derived from a virus and modified by means of molecular biology techniques in a way as to retain some, but not all, the parental virus genes; if the genes responsible for virus replication capacity are deleted, the vector is made replication-incompetent.
What is Worst case?
A condition or set of conditions encompassing upper and lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.
What is Working cell bank (wcb)?
A homogeneous pool of micro-organisms or cells, that are distributed uniformly into a number of containers derived from a MCB that are stored in such a way to ensure stability and for use in production. Working virus seed (WVS) – as above but in relation to viruses, working transgenic bank – as above but for transgenic plants or animals.
What is Yield, expected?
The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale, or manufacturing data.
What is Yield, theoretical?
The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production.
What is Zoonosis?
Animal diseases that can be transmitted to humans