P
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, thebulk product being the filled, but not finally packaged, primary containers.
[EU GMP Guide, Glossary; Main Principles for Pharmaceutical Products, WHO; PIC/S PE 010-4]
Packaging Batch Record
(fiche d'emballage de lot de fabrication) Records demonstrating that the batch of a drug was packaged in accordance with the approved master production documents. [Canadian GMP Guidelines 2009]
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. [EU GMP Guide, Glossary; PIC/S PE 010-4]
Any material intended to protect an intermediate or API during storage and transport.
[EU GMP Guide, Part II; ICH Q7]
Any material, including printed material, employed in the packaging of a pharmaceutical product, but 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. [Guide to Good Storage Practices for Pharmaceuticals, WHO; Main Principles for Pharmaceutical Products, WHO]
Labels, printed packaging materials and those components in direct contact with the dosage form. (refer to C.02.002) [Canadian GMP Guidelines 2009]
Parallel Market
see Unauthorized Market
Parametric Release
A system of release that gives the assurance that the product is of the intended quality based on information collected during the manufacturing process and on the compliance with specific GMP requirements related to Parametric Release. [EU GMP Guide, Annex 17]
Parametric release is one type of RTR testing. Parametric release is based on process data (e.g., temperature, pressure, time for terminal sterilization, physiochemical indicator) rather than the testing of material and/or sample for specific attribute. [ICH Q8, Q&A]
(libération en fonction de paramètre) A validated system of release that gives the assurance that the product is of the intended quality based on information collected during the manufacturing process and on the compliance with specific GMP requirements related to Parametric Release. [Canada GMP Guidelines 2009, Annex 5]
Parental Cell
Cell to be manipulated to give rise to a cell substrate or an intermediate cell line. For microbial expression systems, it is typical to also describe the parental cells as the host cell. For hybridomas, it is typical to also describe the parental cells as the cells to be fused. [ICH Q5D]
Parental Use
(usage parentéral) Administration of a drug by means of hypodermic syringe, needle or other instrument through or into the skin or mucous membrane. [Canadian GMP Guidelines 2009]
Pedigree
A complete record that traces the ownership of and transactions relating to a pharmaceutical product as it is distributed through the supply chain. [Good Distribution Practices for Pharmaceutical Products, WHO]
Percentage of Theoretical Yield
The ratio of the Actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. [21 CFR Part 210, FDA]
Performance Indicator
Measurable values used to quantify quality objectives to reflect the performance of an organisation, process or system, also known as “performance metrics” in some regions. [ICH Q10]
Performance Qualification (PQ)
The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification. [EU GMP Guide, Annex 15]
Permitted Daily Exposure (PDE)
The maximum acceptable intake per day of residual solvent in pharmaceutical products. [ICH Q3C]
Pharmaceutical
All products related to pharmacy, including starting materials (active pharmaceutical ingredients and excipients), finished dosage forms, and biological and other specific products. [Hazard and Risk Analysis, WHO]
Pharmaceutical Excipient
Substances, other than the active ingredient, which have been appropriately evaluated for safety and are included in a drug delivery system to:
Pharmaceutical Isolator
A containment device which utilises barrier technology to provide an enclosed, controlled workspace. [PIC/S PE 010-4]
An arrangement of physical barriers that are integrated to the extent that the isolator can be sealed in order to carry out a routine leak test based on pressure to meet specified limits. Internally it provides a workspace, which is separated from the surrounding environment. Manipulations can be carried out within the space from the outside without compromising its integrity. [PIC/S PI 014-3]
Pharmaceutical Product
Any material or product intended for human or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in the exporting state and/or the importing state. [Main Principles for Pharmaceutical Products, WHO]
Any medicine intended for human use or veterinary product administered to food-producing animals, presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in both the exporting state and the importing state. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Any product intended for human use, or veterinary product intended for administration to food-producing animals, presented in its finished dosage form, which is subject to control by pharmaceutical legislation in either the exporting or the importing state and includes products for which a prescription is required, products which may be sold to patients without a prescription, biologicals and vaccines. It does not, however, include medical devices. [Good Distribution Practices for Pharmaceutical Products, WHO]
Any substance or combination of substances which has a therapeutic, prophylactic or diagnostic purpose, or is intended to modify physiological functions, and is presented in a dosage form suitable for administration to humans. [Specific Pharmaceutical Products, WHO]
Pharmaceutical Quality System (PQS)
Management system to direct and control a pharmaceutical company with regard to quality. [ICH Q10]
Pharmacist
A holder of a degree or diploma in pharmacy from a recognized higher institution of learning and is registered or licensed to practise pharmacy. [Inspection, WHO]
Pharmacopoeial Discussion Group (PDG)
The three-party Pharmacopoeial Discussion Group consisting of representatives from the European Directorate for the Quality of Medicines (EDQM) in the Council of Europe, the Ministry of Health, Labour and Welfare (MHLW) of Japan, and the United States Pharmacopoeial Convention, Inc (USP). [ICH Q4B]
Pharmacopoeial Text
The pharmacopoeial monographs, general test chapters, and analytical methods emanating from the three regional pharmacopoeias. [ICH Q4B]
Pharmacovigilance System
A system used by the marketing authorisation holder and by Member States to fulfil the tasks and responsibilities listed in Title IX and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance. [Directive 2001/83/EC]
Pharmacovigilance System Master File
A detailed description of the pharmacovigilance system used by the marketing authorisation holder with respect to one or more authorised medicinal products. [Directive 2001/83/EC]
Phase 1 Investigational Drug
A new drug or biological drug that is used in phase 1 of a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Pilot Plant Scale
The production of the drug substance or drug product by a procedure fully representative of and simulating that to be applied at manufacturing scale. The methods of cell expansion, harvest, and product purification should be identical except for the scale of production. [ICH Q5C]
Pilot Scale Batch
A batch of a drug substance or drug product manufactured by a procedure fully representative of and simulating that to be applied to a full production scale batch. For solid oral dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100,000 tablets or capsules, whichever is the larger. [ICH Q1A]
Piping & Instrument Diagrams (P&IDs)
Engineering schematic drawings that provide details of the interrelationship of equipment, services, material flows, plant controls and alarms. The P&ID also provide the reference for each tag or label used for identification. [PIC/S PI 006-3]
Plant Functional Specification
Specifications that document functions, standards and permitted tolerances of systems (plant) or system components (equipment) and which define the operating capabilities of the equipment. [PIC/S PI 006-3]
Plasma
The fluid portion of whole blood collected, stabilized against clotting and separated from the red blood cells. [Canadian GMP Guidelines, Annex 14]
Plasmapheresis
Separation of plasma from whole blood and the continuous or intermittent return of red blood cells and formed elements to the donor. Plasma collected by plasmapheresis may be used either as source plasma for further manufacturing or fresh frozen plasma for transfusion. [Canadian GMP Guidelines, Annex 14]
Plateletpheresis
Separation of platelets from whole blood and the continuous or intermittent return of red blood cells, with or without platelet-reduced plasma, to the donor. If plasma is collected as a final product during plateletpheresis, the regulations for plasmapheresis apply. [Canadian GMP Guidelines, Annex 14]
Platform Manufacturing
The approach of developing a production strategy for a new drug starting from manufacturing processes similar to those used by the same applicant to manufacture other drugs of the same type (e.g., as in the production of monoclonal antibodies using predefined host cell, cell culture, and purification processes, for which there already exists considerable experience). [ICH Q11]
Polymorphic Form
Different crystalline forms of the same drug substance. These can include solvation or hydration products (also known as pseudo-polymorphs) and amorphous forms. [ICH Q3A]
Polymorphism
The occurrence of different crystalline forms of the same drug substance. This may include solvation or hydration products (also known as pseudopolymorphs) and amorphous forms. [ICH Q6A]
Positive Control
Refers to the sterility test controls that may be used to define a "false negative" test result. An absence of growth of test challenge micro-organisms in the growth promotion, validation or "stasis" tests would result in a "false negative" test finding and an invalid test result. [PIC/S PI 012-3]
Positron Emitting Radiopharmaceutical (PER)
Drugs labelled with positron emitting radionuclides or containing positron emitting radionuclides that exhibit spontaneous transformation of unstable nuclei through positron decay. [Canadian GMP Guidelines, Annex 5]
Post Donation Information (PDI)
Information related to a donor or a donation made available to the collection facility following a donation. The information can be provided by the donor or other source. It may adversely affect the safety and/or quality of the donated blood/component. PDI does not include errors, accidents or anomalies that occur during screening or later during collection, processing or testing but are discovered at some point after the donation is made. [Canadian GMP Guidelines, Annex 14]
Potency
The measure of the biological activity using a suitably quantitative biological assay (also called potency assay or bioassay), based on the attribute of the product which is linked to the relevant biological properties. [ICH Q6B]
The activity or amount of active moiety, or any form thereof, indicated by label claim to be present. [Canadian GMP Guidelines 2009]
Potential Impurity
An impurity that theoretically can arise during manufacture or storage. It may or may not actually appear in the new drug substance. [ICH Q3A]
Pre-Approval Batch
Pilot or laboratory-scale batches, upon which the application is based, e.g. batches used for pivotal clinical trials and/or those used for bioavailability, bioequivalence and stability studies, and scale-up batches. [Inspection, WHO]
Pre-Determined Acceptance Criteria
The criteria assigned, before undertaking testing, to allow evaluation of test results to demonstrate compliance with a test phase of delivery requirement. [PIC/S PI 006-3]
Precision
The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
Precision should be investigated using homogeneous, authentic samples. However, if it is not possible to obtain a homogeneous sample it may be investigated using artificially prepared samples or a sample solution. The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements. [ICH Q2]
Precursor
A chemical substance or molecule which exists as an ingredient, reactant, or intermediate that is used for the chemical or radiochemical synthesis of a particular desired end product. [Canadian GMP Guidelines 2009, Annex 5]
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. [EU GMP Guide, Annex 3]
All operations of purchase of materials and products, production, quality control, release, storage, delivery of medicinal products and the related controls. Note: The simple provisioning of medicinal products according to authorised instructions and without necessitating pharmaceutical technical knowledge, where medicinal products are made ready for immediate application (e.g. dissolution of a powder for immediate application according to the instructions in the package leaflet of an authorised product), is normally not normally considered as preparation. [PIC/S PE 010-4]
Prequalification
The activities undertaken in defining a product or service need, seeking expressions of interest from enterprises to supply the product or service, and examining the product or service offered against the specification, and the facility where the product or service is prepared against common standards of good manufacturing practice (GMP). The examination of the product or service and of the facility where it is manufactured is performed by trained and qualified inspectors against common standards. Once the product is approved, and the facility is approved for the delivery of the specified product or service, other procurement agencies are informed of the approval. Prequalification is required for all pharmaceutical products regardless of their composition and place of manufacture or registration, but the amount and type of information requested from the supplier for use in the assessment by the procurement agency may differ. [Sampling Operations, WHO]
Pressure Cascade
A process whereby air flows from one area, which is maintained at a higher pressure, to another area at a lower pressure. [Main Principles for Pharmaceutical Products, WHO]
Preventive Action
Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. Note: Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the cause of a potential discrepancy or other undesirable situation to prevent such an occurrence. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Primary Batch
A batch of a drug substance or drug product used in a formal stability study, from which stability data are submitted in a registration application for the purpose of establishing a re-test period or shelf life, respectively. A primary batch of a drug substance should be at least a pilot scale batch. For a drug product, two of the three batches should be at least pilot scale batch, and the third batch can be smaller if it is representative with regard to the critical manufacturing steps. However, a primary batch may be a production batch. [ICH Q1A]
Primary Containment
A containment system that prevents the escape of a biological agent into the immediate working environment. This includes the use of closed containers or biological safety workstations together with safe working procedures. See also containment. [EU GMP Guide, Glossary]
Principal Investigator
The responsible leader of the team if a trial is conducted by a team of individual investigators at a trial site Investigator. [EU GMP Guide, Annex 13]
Procedural Control
Manufacturing methodologies executed in such a manner as to prevent or minimize contamination. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Procedure
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. [EU GMP Guide, Glossary, ICH Q7]
Process Aid
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). [EU GMP Guide, Part II, ICH Q7]
This refers to the materials (e.g. filter aid, activated carbon, etc, excluding solvents), used as an aid in the production of an intermediate or API that do not participate in a chemical or biological reaction itself. [Chinese GMP Guidelines, Annex 2]
Process Analytical Technologie (PAT)
System for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality. [ICHQ8, PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance, FDA]
Process Capability Index
A process capability index CpK represents the true measure of process capability
CpK = (X – LSL)/3s
or = (USL – X)/3s
where
LSL = Lower specification limit
USL= Upper specification limit
X = Mean
s = Standard deviation
[PIC/S PI 006-3]
Process Capability Study
A process capability study is a statistical method that compares process information (e.g. X and s) to the upper and lower specification limits. [PIC/S PI 006-3]
Process Characterisation of Viral Clearance
Viral clearance studies in which non-specific “model” viruses are used to assess the robustness of the manufacturing process to remove and/or inactivate viruses. [ICH Q5A]
Process Design
Defining the commercial manufacturing process based on knowledge gained through development and scale-up activities. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Process Evaluation Studies of Viral Clearance
Viral clearance studies in which “relevant” and/or specific “model” viruses are used to determine the ability of the manufacturing process to remove and/or inactivate these viruses. [ICH Q5A]
Process Performance Qualification (PPQ)
Establishing confidence that the process is effective and reproducible. [Guideline on General Principles of Process Validation, FDA]
Process Qualification
Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Process Robustness
Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality. [ICH Q8, TRS 981 Annex 2, WHO]
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. [EU GMP Guide, Annex 15]
Documented evidence which provides a high degree of assurance that a specific process will consistently result in a product that meets its predetermined specifications and quality characteristics. [Main Principles for Pharmaceutical Products, WHO]
Documented verification that the integrated system functions as intended, in its normal operating environment. (The term Performance Qualification may be used also). Note: Processes may be proven also by documented verification through appropriate testing that the finished product produced by a specified process meets all release requirements. This may be called Product Qualification. [PIC/S PI 006-3]
Establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications. [21 CFR Part 820, FDA]
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Establishing documented evidence with a high degree of assurance, that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. Process validation may take the form of Prospective, Concurrent or Retrospective Validation and Process Qualification or Re-validation. [Canadian GMP Guidelines 2009]
Process-related Impurity
Impurities that are derived from the manufacturing process. They may be derived from cell substrates (e.g., host cell proteins, host cell DNA), cell culture (e.g., inducers, antibiotics, or media components), or downstream processing (e.g., processing reagents or column leachables). [ICH Q6B]
Processing
That part of the preparation of a medicinal product involving the dosage form. [PIC/S PE 010-4] Any fabricating step performed between the collection of blood and the issuing of a component. [Canadian GMP Guidelines, Annex 14]
Procuring
Obtaining, acquiring, purchasing or buying medicinal products from manufacturers, importers or other wholesale distributors. [EU GDP Guidelines]
Product
Components, manufacturing materials, in- process devices, finished devices, and returned devices. [21 CFR Part 820, FDA]
Product Lifecycle
All phases in the life of the product from the initial development through marketing until the product's discontinuation. [ICH Q9]
Product Performance Qualification
Establishing confidence through appropriate testing that the finished product produced by a specified process meets all release requirements for functionality and safety. [Guideline on General Principles of Process Validation, FDA]
Product Quality Review (PQR)
Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews. [EU GMP Guide, Part I]
Regular quality reviews of APIs should be conducted with the objective of verifying the consistency of the process. Such reviews should normally be conducted and documented annually. [EU GMP Guide, Part II]
Product Realisation
Achievement of a product with the quality attributes appropriate to meet the needs of patients, health care professionals, and regulatory authorities (including compliance with marketing authorisation) and internal customers requirements. [ICH Q10]
Product Recall
A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency. [Good Distribution Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Product Specification File (PSF)
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. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Product-related Impurity
Molecular variants of the desired product (e.g., precursors, certain degradation products arising during manufacture and/or storage) which do not have properties comparable to those of the desired product with respect to activity, efficacy, and safety. [ICH Q6B]
Product-related Substance
Molecular variants of the desired product formed during manufacture and/or storage which are active and have no deleterious effect on the safety and efficacy of the drug product. These variants possess properties comparable to the desired product and are not considered impurities. [ICH Q6B]
Product-specific Cleaning
(nettoyage adapté au produit) Cleaning procedure performed to ensure removal of product residuals from non-dedicated product-contact equipment/ containers which includes appropriate assays to validate the effectiveness of the cleaning. [Canadian GMP Guidelines, Annex 2]
Product/ Service
The intended results of activities or processes, products/services can be tangible or intangible. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Production
see Manufacture
Production Batch
A batch of a drug substance or drug product manufactured at production scale by using production equipment in a production facility as specified in the application. [ICH Q1A]
Production Cell
Cell substrate used to manufacture product. [ICH Q5A]
Cell substrate used to fabricate the product. [Canadian GMP Guidelines 2009, Annex 2]
Production Supervisor
The person responsible for supervision should be in the department where the production takes place. He/she should be aware of what is going on and able to ensure that the process is carried out in the prescribed manner. [PIC/S PE 010-4]
Prohibited Drug
These are drugs with toxicity or side-effects that outweigh their therapeutic usefulness, so that public health and welfare are protected by prohibiting their production, manufacture, export, import, trade, distribution, supply, possession or use, except in amounts required for medical and scientific research. Prohibited drugs are normally determined by the national or supranational registration/ licensing authority. [Inspection, WHO]
Prospective Validation
Validation carried out before routine production of products intended for sale. [EU GMP Guide, Annex 15]
Validation carried out during the development stage on the basis of a risk analysis of the production process, which is broken down into individual steps, these are then evaluated on the basis of past experience to determine whether they may lead to critical situations. [Main Principles for Pharmaceutical Products, WHO]
Establishing documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol. [PIC/S PI 006-3]
Protocol
A document that describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments. [Directive 2001/20/EC]
A document which gives the background, rationale and objectives of the trial and describes its design, methodology and organization, including statistical considerations, and the conditions under which it is to be performed and managed. It should be dated and signed by the investigator/institution involved and the sponsor, and can, in addition, function as a contract. [Good Manufacturing Practices: Specific Pharmaceutical Products, WHO]
Proven Acceptable Range (PAR)
A characterised range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria. [ICH Q8]
Public Key Infrastructure, PKI
Public Key Infrastructure (PKI) provides a framework for secure communication, using a combination of public-key cryptography and Digital Certificates. PKIs can exist within many different domains but essentially there are two types: public PKI and private PKI. [PIC/S PI 011-3]
Public Key Infrastructure, private
is deployed by a corporation for the benefit of its business and any related parties (e.g. customers, suppliers). [PIC/S PI 011-3]
Public Key Infrastructure, public
(using ‘Trusted Third Parties’) are deployed on open systems, such as the Internet and facilitate security between previously unrelated parties. [PIC/S PI 011-3]
Public Service Obligation
The obligation placed on wholesalers to guarantee permanently an adequate range of medicinal products to meet the requirements of a specific geographical area and to deliver the supplies requested within a very short time over the whole of the area in question. [Directive 2001/83/EC]
Pure Culture
(culture pure) A culture broth/ medium containing a single type of microorganism. [Canadian GMP Guidelines, Annex 2]
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. [EU GMP Guide, Annex 6]
Purified Water
Demineralised water, deionised water. [Pharmacopoea Europaea]
Purity
The extent to which a raw material or a drug in dosage form is free from undesirable or adulterating chemical, biological, or physical entities as defined by specifications. [Canadian GMP Guidelines 2009]
Purity Test
To ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte, i.e. related substances test, heavy metals, residual solvents content, etc. [ICH Q2]
Pyrogen
A substance that induces a febrile reaction in a patient. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
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, thebulk product being the filled, but not finally packaged, primary containers.
[EU GMP Guide, Glossary; Main Principles for Pharmaceutical Products, WHO; PIC/S PE 010-4]
Packaging Batch Record
(fiche d'emballage de lot de fabrication) Records demonstrating that the batch of a drug was packaged in accordance with the approved master production documents. [Canadian GMP Guidelines 2009]
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. [EU GMP Guide, Glossary; PIC/S PE 010-4]
Any material intended to protect an intermediate or API during storage and transport.
[EU GMP Guide, Part II; ICH Q7]
Any material, including printed material, employed in the packaging of a pharmaceutical product, but 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. [Guide to Good Storage Practices for Pharmaceuticals, WHO; Main Principles for Pharmaceutical Products, WHO]
Labels, printed packaging materials and those components in direct contact with the dosage form. (refer to C.02.002) [Canadian GMP Guidelines 2009]
Parallel Market
see Unauthorized Market
Parametric Release
A system of release that gives the assurance that the product is of the intended quality based on information collected during the manufacturing process and on the compliance with specific GMP requirements related to Parametric Release. [EU GMP Guide, Annex 17]
Parametric release is one type of RTR testing. Parametric release is based on process data (e.g., temperature, pressure, time for terminal sterilization, physiochemical indicator) rather than the testing of material and/or sample for specific attribute. [ICH Q8, Q&A]
(libération en fonction de paramètre) A validated system of release that gives the assurance that the product is of the intended quality based on information collected during the manufacturing process and on the compliance with specific GMP requirements related to Parametric Release. [Canada GMP Guidelines 2009, Annex 5]
Parental Cell
Cell to be manipulated to give rise to a cell substrate or an intermediate cell line. For microbial expression systems, it is typical to also describe the parental cells as the host cell. For hybridomas, it is typical to also describe the parental cells as the cells to be fused. [ICH Q5D]
Parental Use
(usage parentéral) Administration of a drug by means of hypodermic syringe, needle or other instrument through or into the skin or mucous membrane. [Canadian GMP Guidelines 2009]
Pedigree
A complete record that traces the ownership of and transactions relating to a pharmaceutical product as it is distributed through the supply chain. [Good Distribution Practices for Pharmaceutical Products, WHO]
Percentage of Theoretical Yield
The ratio of the Actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. [21 CFR Part 210, FDA]
Performance Indicator
Measurable values used to quantify quality objectives to reflect the performance of an organisation, process or system, also known as “performance metrics” in some regions. [ICH Q10]
Performance Qualification (PQ)
The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification. [EU GMP Guide, Annex 15]
Permitted Daily Exposure (PDE)
The maximum acceptable intake per day of residual solvent in pharmaceutical products. [ICH Q3C]
Pharmaceutical
All products related to pharmacy, including starting materials (active pharmaceutical ingredients and excipients), finished dosage forms, and biological and other specific products. [Hazard and Risk Analysis, WHO]
Pharmaceutical Excipient
Substances, other than the active ingredient, which have been appropriately evaluated for safety and are included in a drug delivery system to:
- aid in the processing of the drug delivery system during its manufacture,
- protect, support or enhance stability, bioavailability, or patient acceptability,
- assist in product identification, or
- fenhance any other attribute of the overall safety and effectiveness of the drug during storage or use. [Starting Materials, WHO]
Pharmaceutical Isolator
A containment device which utilises barrier technology to provide an enclosed, controlled workspace. [PIC/S PE 010-4]
An arrangement of physical barriers that are integrated to the extent that the isolator can be sealed in order to carry out a routine leak test based on pressure to meet specified limits. Internally it provides a workspace, which is separated from the surrounding environment. Manipulations can be carried out within the space from the outside without compromising its integrity. [PIC/S PI 014-3]
Pharmaceutical Product
Any material or product intended for human or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in the exporting state and/or the importing state. [Main Principles for Pharmaceutical Products, WHO]
Any medicine intended for human use or veterinary product administered to food-producing animals, presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in both the exporting state and the importing state. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Any product intended for human use, or veterinary product intended for administration to food-producing animals, presented in its finished dosage form, which is subject to control by pharmaceutical legislation in either the exporting or the importing state and includes products for which a prescription is required, products which may be sold to patients without a prescription, biologicals and vaccines. It does not, however, include medical devices. [Good Distribution Practices for Pharmaceutical Products, WHO]
Any substance or combination of substances which has a therapeutic, prophylactic or diagnostic purpose, or is intended to modify physiological functions, and is presented in a dosage form suitable for administration to humans. [Specific Pharmaceutical Products, WHO]
Pharmaceutical Quality System (PQS)
Management system to direct and control a pharmaceutical company with regard to quality. [ICH Q10]
Pharmacist
A holder of a degree or diploma in pharmacy from a recognized higher institution of learning and is registered or licensed to practise pharmacy. [Inspection, WHO]
Pharmacopoeial Discussion Group (PDG)
The three-party Pharmacopoeial Discussion Group consisting of representatives from the European Directorate for the Quality of Medicines (EDQM) in the Council of Europe, the Ministry of Health, Labour and Welfare (MHLW) of Japan, and the United States Pharmacopoeial Convention, Inc (USP). [ICH Q4B]
Pharmacopoeial Text
The pharmacopoeial monographs, general test chapters, and analytical methods emanating from the three regional pharmacopoeias. [ICH Q4B]
Pharmacovigilance System
A system used by the marketing authorisation holder and by Member States to fulfil the tasks and responsibilities listed in Title IX and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance. [Directive 2001/83/EC]
Pharmacovigilance System Master File
A detailed description of the pharmacovigilance system used by the marketing authorisation holder with respect to one or more authorised medicinal products. [Directive 2001/83/EC]
Phase 1 Investigational Drug
A new drug or biological drug that is used in phase 1 of a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Pilot Plant Scale
The production of the drug substance or drug product by a procedure fully representative of and simulating that to be applied at manufacturing scale. The methods of cell expansion, harvest, and product purification should be identical except for the scale of production. [ICH Q5C]
Pilot Scale Batch
A batch of a drug substance or drug product manufactured by a procedure fully representative of and simulating that to be applied to a full production scale batch. For solid oral dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100,000 tablets or capsules, whichever is the larger. [ICH Q1A]
Piping & Instrument Diagrams (P&IDs)
Engineering schematic drawings that provide details of the interrelationship of equipment, services, material flows, plant controls and alarms. The P&ID also provide the reference for each tag or label used for identification. [PIC/S PI 006-3]
Plant Functional Specification
Specifications that document functions, standards and permitted tolerances of systems (plant) or system components (equipment) and which define the operating capabilities of the equipment. [PIC/S PI 006-3]
Plasma
The fluid portion of whole blood collected, stabilized against clotting and separated from the red blood cells. [Canadian GMP Guidelines, Annex 14]
Plasmapheresis
Separation of plasma from whole blood and the continuous or intermittent return of red blood cells and formed elements to the donor. Plasma collected by plasmapheresis may be used either as source plasma for further manufacturing or fresh frozen plasma for transfusion. [Canadian GMP Guidelines, Annex 14]
Plateletpheresis
Separation of platelets from whole blood and the continuous or intermittent return of red blood cells, with or without platelet-reduced plasma, to the donor. If plasma is collected as a final product during plateletpheresis, the regulations for plasmapheresis apply. [Canadian GMP Guidelines, Annex 14]
Platform Manufacturing
The approach of developing a production strategy for a new drug starting from manufacturing processes similar to those used by the same applicant to manufacture other drugs of the same type (e.g., as in the production of monoclonal antibodies using predefined host cell, cell culture, and purification processes, for which there already exists considerable experience). [ICH Q11]
Polymorphic Form
Different crystalline forms of the same drug substance. These can include solvation or hydration products (also known as pseudo-polymorphs) and amorphous forms. [ICH Q3A]
Polymorphism
The occurrence of different crystalline forms of the same drug substance. This may include solvation or hydration products (also known as pseudopolymorphs) and amorphous forms. [ICH Q6A]
Positive Control
Refers to the sterility test controls that may be used to define a "false negative" test result. An absence of growth of test challenge micro-organisms in the growth promotion, validation or "stasis" tests would result in a "false negative" test finding and an invalid test result. [PIC/S PI 012-3]
Positron Emitting Radiopharmaceutical (PER)
Drugs labelled with positron emitting radionuclides or containing positron emitting radionuclides that exhibit spontaneous transformation of unstable nuclei through positron decay. [Canadian GMP Guidelines, Annex 5]
Post Donation Information (PDI)
Information related to a donor or a donation made available to the collection facility following a donation. The information can be provided by the donor or other source. It may adversely affect the safety and/or quality of the donated blood/component. PDI does not include errors, accidents or anomalies that occur during screening or later during collection, processing or testing but are discovered at some point after the donation is made. [Canadian GMP Guidelines, Annex 14]
Potency
The measure of the biological activity using a suitably quantitative biological assay (also called potency assay or bioassay), based on the attribute of the product which is linked to the relevant biological properties. [ICH Q6B]
The activity or amount of active moiety, or any form thereof, indicated by label claim to be present. [Canadian GMP Guidelines 2009]
Potential Impurity
An impurity that theoretically can arise during manufacture or storage. It may or may not actually appear in the new drug substance. [ICH Q3A]
Pre-Approval Batch
Pilot or laboratory-scale batches, upon which the application is based, e.g. batches used for pivotal clinical trials and/or those used for bioavailability, bioequivalence and stability studies, and scale-up batches. [Inspection, WHO]
Pre-Determined Acceptance Criteria
The criteria assigned, before undertaking testing, to allow evaluation of test results to demonstrate compliance with a test phase of delivery requirement. [PIC/S PI 006-3]
Precision
The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
Precision should be investigated using homogeneous, authentic samples. However, if it is not possible to obtain a homogeneous sample it may be investigated using artificially prepared samples or a sample solution. The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements. [ICH Q2]
Precursor
A chemical substance or molecule which exists as an ingredient, reactant, or intermediate that is used for the chemical or radiochemical synthesis of a particular desired end product. [Canadian GMP Guidelines 2009, Annex 5]
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. [EU GMP Guide, Annex 3]
All operations of purchase of materials and products, production, quality control, release, storage, delivery of medicinal products and the related controls. Note: The simple provisioning of medicinal products according to authorised instructions and without necessitating pharmaceutical technical knowledge, where medicinal products are made ready for immediate application (e.g. dissolution of a powder for immediate application according to the instructions in the package leaflet of an authorised product), is normally not normally considered as preparation. [PIC/S PE 010-4]
Prequalification
The activities undertaken in defining a product or service need, seeking expressions of interest from enterprises to supply the product or service, and examining the product or service offered against the specification, and the facility where the product or service is prepared against common standards of good manufacturing practice (GMP). The examination of the product or service and of the facility where it is manufactured is performed by trained and qualified inspectors against common standards. Once the product is approved, and the facility is approved for the delivery of the specified product or service, other procurement agencies are informed of the approval. Prequalification is required for all pharmaceutical products regardless of their composition and place of manufacture or registration, but the amount and type of information requested from the supplier for use in the assessment by the procurement agency may differ. [Sampling Operations, WHO]
Pressure Cascade
A process whereby air flows from one area, which is maintained at a higher pressure, to another area at a lower pressure. [Main Principles for Pharmaceutical Products, WHO]
Preventive Action
Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. Note: Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. [ISO 9000:2005, ICH Q10]
Action taken to eliminate the cause of a potential discrepancy or other undesirable situation to prevent such an occurrence. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Primary Batch
A batch of a drug substance or drug product used in a formal stability study, from which stability data are submitted in a registration application for the purpose of establishing a re-test period or shelf life, respectively. A primary batch of a drug substance should be at least a pilot scale batch. For a drug product, two of the three batches should be at least pilot scale batch, and the third batch can be smaller if it is representative with regard to the critical manufacturing steps. However, a primary batch may be a production batch. [ICH Q1A]
Primary Containment
A containment system that prevents the escape of a biological agent into the immediate working environment. This includes the use of closed containers or biological safety workstations together with safe working procedures. See also containment. [EU GMP Guide, Glossary]
Principal Investigator
The responsible leader of the team if a trial is conducted by a team of individual investigators at a trial site Investigator. [EU GMP Guide, Annex 13]
Procedural Control
Manufacturing methodologies executed in such a manner as to prevent or minimize contamination. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Procedure
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. [EU GMP Guide, Glossary, ICH Q7]
Process Aid
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). [EU GMP Guide, Part II, ICH Q7]
This refers to the materials (e.g. filter aid, activated carbon, etc, excluding solvents), used as an aid in the production of an intermediate or API that do not participate in a chemical or biological reaction itself. [Chinese GMP Guidelines, Annex 2]
Process Analytical Technologie (PAT)
System for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality. [ICHQ8, PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance, FDA]
Process Capability Index
A process capability index CpK represents the true measure of process capability
CpK = (X – LSL)/3s
or = (USL – X)/3s
where
LSL = Lower specification limit
USL= Upper specification limit
X = Mean
s = Standard deviation
[PIC/S PI 006-3]
Process Capability Study
A process capability study is a statistical method that compares process information (e.g. X and s) to the upper and lower specification limits. [PIC/S PI 006-3]
Process Characterisation of Viral Clearance
Viral clearance studies in which non-specific “model” viruses are used to assess the robustness of the manufacturing process to remove and/or inactivate viruses. [ICH Q5A]
Process Design
Defining the commercial manufacturing process based on knowledge gained through development and scale-up activities. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Process Evaluation Studies of Viral Clearance
Viral clearance studies in which “relevant” and/or specific “model” viruses are used to determine the ability of the manufacturing process to remove and/or inactivate these viruses. [ICH Q5A]
Process Performance Qualification (PPQ)
Establishing confidence that the process is effective and reproducible. [Guideline on General Principles of Process Validation, FDA]
Process Qualification
Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Process Robustness
Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality. [ICH Q8, TRS 981 Annex 2, WHO]
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. [EU GMP Guide, Annex 15]
Documented evidence which provides a high degree of assurance that a specific process will consistently result in a product that meets its predetermined specifications and quality characteristics. [Main Principles for Pharmaceutical Products, WHO]
Documented verification that the integrated system functions as intended, in its normal operating environment. (The term Performance Qualification may be used also). Note: Processes may be proven also by documented verification through appropriate testing that the finished product produced by a specified process meets all release requirements. This may be called Product Qualification. [PIC/S PI 006-3]
Establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications. [21 CFR Part 820, FDA]
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. [Guidance for Industry: Process Validation: General Principles and Practices, FDA]
Establishing documented evidence with a high degree of assurance, that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. Process validation may take the form of Prospective, Concurrent or Retrospective Validation and Process Qualification or Re-validation. [Canadian GMP Guidelines 2009]
Process-related Impurity
Impurities that are derived from the manufacturing process. They may be derived from cell substrates (e.g., host cell proteins, host cell DNA), cell culture (e.g., inducers, antibiotics, or media components), or downstream processing (e.g., processing reagents or column leachables). [ICH Q6B]
Processing
That part of the preparation of a medicinal product involving the dosage form. [PIC/S PE 010-4] Any fabricating step performed between the collection of blood and the issuing of a component. [Canadian GMP Guidelines, Annex 14]
Procuring
Obtaining, acquiring, purchasing or buying medicinal products from manufacturers, importers or other wholesale distributors. [EU GDP Guidelines]
Product
Components, manufacturing materials, in- process devices, finished devices, and returned devices. [21 CFR Part 820, FDA]
Product Lifecycle
All phases in the life of the product from the initial development through marketing until the product's discontinuation. [ICH Q9]
Product Performance Qualification
Establishing confidence through appropriate testing that the finished product produced by a specified process meets all release requirements for functionality and safety. [Guideline on General Principles of Process Validation, FDA]
Product Quality Review (PQR)
Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews. [EU GMP Guide, Part I]
Regular quality reviews of APIs should be conducted with the objective of verifying the consistency of the process. Such reviews should normally be conducted and documented annually. [EU GMP Guide, Part II]
Product Realisation
Achievement of a product with the quality attributes appropriate to meet the needs of patients, health care professionals, and regulatory authorities (including compliance with marketing authorisation) and internal customers requirements. [ICH Q10]
Product Recall
A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency. [Good Distribution Practices for Pharmaceutical Products, WHO, Inspection, WHO]
Product Specification File (PSF)
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. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Product-related Impurity
Molecular variants of the desired product (e.g., precursors, certain degradation products arising during manufacture and/or storage) which do not have properties comparable to those of the desired product with respect to activity, efficacy, and safety. [ICH Q6B]
Product-related Substance
Molecular variants of the desired product formed during manufacture and/or storage which are active and have no deleterious effect on the safety and efficacy of the drug product. These variants possess properties comparable to the desired product and are not considered impurities. [ICH Q6B]
Product-specific Cleaning
(nettoyage adapté au produit) Cleaning procedure performed to ensure removal of product residuals from non-dedicated product-contact equipment/ containers which includes appropriate assays to validate the effectiveness of the cleaning. [Canadian GMP Guidelines, Annex 2]
Product/ Service
The intended results of activities or processes, products/services can be tangible or intangible. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
Production
see Manufacture
Production Batch
A batch of a drug substance or drug product manufactured at production scale by using production equipment in a production facility as specified in the application. [ICH Q1A]
Production Cell
Cell substrate used to manufacture product. [ICH Q5A]
Cell substrate used to fabricate the product. [Canadian GMP Guidelines 2009, Annex 2]
Production Supervisor
The person responsible for supervision should be in the department where the production takes place. He/she should be aware of what is going on and able to ensure that the process is carried out in the prescribed manner. [PIC/S PE 010-4]
Prohibited Drug
These are drugs with toxicity or side-effects that outweigh their therapeutic usefulness, so that public health and welfare are protected by prohibiting their production, manufacture, export, import, trade, distribution, supply, possession or use, except in amounts required for medical and scientific research. Prohibited drugs are normally determined by the national or supranational registration/ licensing authority. [Inspection, WHO]
Prospective Validation
Validation carried out before routine production of products intended for sale. [EU GMP Guide, Annex 15]
Validation carried out during the development stage on the basis of a risk analysis of the production process, which is broken down into individual steps, these are then evaluated on the basis of past experience to determine whether they may lead to critical situations. [Main Principles for Pharmaceutical Products, WHO]
Establishing documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol. [PIC/S PI 006-3]
Protocol
A document that describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments. [Directive 2001/20/EC]
A document which gives the background, rationale and objectives of the trial and describes its design, methodology and organization, including statistical considerations, and the conditions under which it is to be performed and managed. It should be dated and signed by the investigator/institution involved and the sponsor, and can, in addition, function as a contract. [Good Manufacturing Practices: Specific Pharmaceutical Products, WHO]
Proven Acceptable Range (PAR)
A characterised range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria. [ICH Q8]
Public Key Infrastructure, PKI
Public Key Infrastructure (PKI) provides a framework for secure communication, using a combination of public-key cryptography and Digital Certificates. PKIs can exist within many different domains but essentially there are two types: public PKI and private PKI. [PIC/S PI 011-3]
Public Key Infrastructure, private
is deployed by a corporation for the benefit of its business and any related parties (e.g. customers, suppliers). [PIC/S PI 011-3]
Public Key Infrastructure, public
(using ‘Trusted Third Parties’) are deployed on open systems, such as the Internet and facilitate security between previously unrelated parties. [PIC/S PI 011-3]
Public Service Obligation
The obligation placed on wholesalers to guarantee permanently an adequate range of medicinal products to meet the requirements of a specific geographical area and to deliver the supplies requested within a very short time over the whole of the area in question. [Directive 2001/83/EC]
Pure Culture
(culture pure) A culture broth/ medium containing a single type of microorganism. [Canadian GMP Guidelines, Annex 2]
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. [EU GMP Guide, Annex 6]
Purified Water
Demineralised water, deionised water. [Pharmacopoea Europaea]
Purity
The extent to which a raw material or a drug in dosage form is free from undesirable or adulterating chemical, biological, or physical entities as defined by specifications. [Canadian GMP Guidelines 2009]
Purity Test
To ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte, i.e. related substances test, heavy metals, residual solvents content, etc. [ICH Q2]
Pyrogen
A substance that induces a febrile reaction in a patient. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]