R
Racemate
A composite (solid, liquid, gaseous, or in solution) of equimolar quantities of two enantiomeric species. It is devoid of optical activity. [ICH Q6A]
Radio Synthesizer Unit (RSU)
A closed-system device for the synthesis of radioactive drug substances used in the manufacturing of PERs. The system may be controlled by graphical computer software programs. [Canadian GMP Guidelines, Annex 5]
Radioactive Concentration
Amount of radioactivity per unit volume such as mCi/ml or MBq/ml. [Canadian GMP Guidelines, Annex 3, Annex 5]
Radioactivity
Spontaneous decay of unstable nuclei and is quantified as the number of disintegrations per unit of time as given in Becquerel (Bq) or Curie (Ci) units. [Canadian GMP Guidelines, Annex 3, Annex 5]
Radionuclide
A nuclide with an unstable or excited nucleus (imbalance of protons and neutrons) which will undergo spontaneous transformation with emissions of subatomic particles and/or photons of energy. [Canadian GMP Guidelines, Annex 3]
Radionuclide Generator
Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be obtained by elution or by any other method used in a radiopharmaceutical. [Directive 2001/83/EC]
Radionuclide PrecursorAny other radionuclide produced for the radio-labelling of another substance prior to administration. [Directive 2001/83/EC]
Radiopharmaceutical
Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [EU GMP Guide, Glossary, Directive 2001/83/EC]
Random Sample
Sample in which the different fractions of the material have an equal probability of being represented. [Sampling Operations, WHO]
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. [EU GMP Guide, Annex13, Canadian GMP Guidelines, Annex 13]
Randomisation Code
A listing in which the treatment assigned to each subject from the randomisation process is identified. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Range
The range of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. [ICH Q2]
Rapidly Dissolving Product
An immediate release solid oral drug product is considered rapidly dissolving when not less than 80% of the label amount of the drug substance dissolves within 15 minutes in each of the following media: (1) pH 1.2, (2) pH 4.0, and (3) pH 6.8. [ICH Q6A]
Raw Data
Any work-sheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities and which are necessary for the reconstruction and evaluation of a work project, process or study report, etc. Raw data may be hard/paper copy or electronic but must be known and defined in system procedures. [PIC/S PI 011-3]
Raw Material
A general term used to denote starting materials, reagents, and solvents intended for use in the production of intermediates or APIs. [EU GMP Guide, Part II, ICH Q7]
Any substance, other than in-process drug or packaging material, intended to be used in the manufacture of drugs, including those that appear in the master formula but that do not appear in the drug such as solvents and processing aids. [Canadian GMP Guidelines 2009]
Reagent
A substance other than a starting material, intermediate, or solvent that is used in the manufacture of a new drug substance. [ICH Q6A, Q3A]
Real-Time Release Testing (RTRT)
The ability to evaluate and ensure the quality of in-process and/or final product based on process data, which typically include a valid combination of measured material attributes and process controls. [ICH Q8]
Receiving Unit (RU)The involved disciplines at an organization where a designated product, process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Reconciliation
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically and actually produced or used. [EU GMP Guide, Glossary]
A comparison between the theoretical quantity and the actual quantity. [Main Principles for Pharmaceutical Products, WHO]
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically produced or used and the amount actually produced or used. [Canadian GMP Guidelines 2009]
Recovered Plasma
The liquid portion of a single donation of whole blood separated from cellular components and intended for further manufacture. [Canadian GMP Guidelines, Annex 14]
Recovery
The introduction of all or part of previous batches (or of redistilled solvents and similar products) of the required quality into another batch at a defined stage of manufacture. It includes the removal of impurities from waste to obtain a pure substance or the recovery of used materials for a separate use. [EU GMP Guide, Glossary, Main Principles for Pharmaceutical Products, WHO, Canadian GMP Guidelines 2009]
Reference Sample (see also Retention Sample)
Sample of a batch of starting material, packaging material or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned. Where stability permits, reference samples from critical intermediate stages (e.g. those requiring analytical testing and release) or intermediates, that are transported outside of the manufacturer’s control, should be kept. [EU GMP Guide, Annex 19]
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. [EU GMP Guide, Part II, ICH Q7]
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. [EU GMP Guide, Part II, ICH Q7]
Regulated User
The regulated Good Practice entity, that is responsible for the operation of a computerised system and the applications, files and data held thereon. [PIC/S PI 011-3]
Regulatory Authority
A government agency or other entity in an MRA country that has a legal right to control the use or sale of drugs within that country and that may take enforcement action to ensure that drugs marketed within its jurisdiction comply with legal requirements. [Canadian GMP Guidelines 2009]
Relative Humidity
The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of the air at the same temperature expressed as a percentage. More simply put, it is the ratio of the mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given temperature. [Main Principles for Pharmaceutical Products, WHO]
Releasing Officer
The person who releases the prepared medicinal products. This person may be the Responsible Person. [PIC/S PE 010-4]
Relevant Genotypic and Phenotypic Marker
Those markers permitting the identification of the strain of the cell line which should include the expression of the recombinant protein or presence of the expression construct. [ICH Q5B]
Relevant Virus
Virus used in process evaluation studies which is either the identified virus, or of the same species as the virus that is known, or likely to contaminate the cell substrate or any other reagents or materials used in the production process. [ICH Q5A]
Remanufacturer
Any person who processes, conditions, renovates, repackages, restores, or does any other act to a finished [medical] device that significantly changes the finished device‘s performance or safety specifications, or intended use. [21 CFR Part 820, FDA]
Repeatability
Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision. [ICH Q2]
Reporting ThresholdA limit above (>) which an impurity should be reported. Reporting threshold is the same as reporting level in Q2B. [ICH Q3A]
A limit above (>) which a degradation product should be reported. [ICH Q3B]
Representative Sample
Sample obtained according to a sampling procedure designed to ensure that the different parts of a batch or the different properties of a non-uniform material are proportionately represented. [Sampling Operations, WHO]
A sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled. [21 CFR Part 210, FDA]
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. [EU GMP Guide, Glossary]
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. [EU GMP Guide, Part II, ICH Q7]
Subjecting all or part of a batch or lot of an in-process drug, bulk process intermediate (final biological bulk intermediate) or bulk product of a single batch/ lot to a previous step in the validated manufacturing process due to failure to meet predetermined specifications. Reprocessing procedures are foreseen as occasionally necessary for biological drugs and, in such cases, are validated and pre-approved as part of the marketing authorization. [Main Principles for Pharmaceutical Products, WHO, Canadian GMP Guidelines 2009]
Reproducibility
Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology). [ICH Q2]
Requirement
The explicit or implicit needs or expectations of the patients or their surrogates (e.g., health care professionals, regulators and legislators). In this document, “requirements” refers not only to statutory, legislative, or regulatory requirements, but also to such needs and expectations. [ICH Q9]
Responsible Person
The person who is ultimately responsible for all aspects of the preparation of medicinal products including the release of these items. This person must have sufficient scientific and technical education and experience to perform this duty. [PICS/S PE 010-4]
Retention Sample (see also Reference Sample)
A sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes. For example, presentation, packaging, labelling, patient information leaflet, batch number, expiry date should the need arise during the shelf life of the batch concerned. There may be exceptional circumstances where this requirement can be met without retention of duplicate samples e.g. where small amounts of a batch are packaged for different markets or in the production of very expensive medicinal products. For finished products, in many instances the reference and retention samples will be presented identically, i.e. as fully packaged units. In such circumstances, reference and retention samples may be regarded as interchangeable [EU GMP Guide, Annex 19]
Sample collected as part of the original sampling process and reserved for future testing. The size of a retention sample should be sufficient to allow for at least two confirmatory analyses. In some cases statutory regulations may require one or more retention samples, each of which should be separately identified, packaged and sealed. [Sampling Operations, WHO]
Retest Date
The date after which samples of the drug substance should be examined to ensure that the material is still in compliance with the specification and thus suitable for use in the manufacture of a given drug product. [ICH Q1A]
The date when a material should be re-examined to ensure that it is still suitable for use. [ICH Q7]
The date when a material should be re-examined to ensure that it is still suitable for use. [EU GMP Guide, Part II, Guide to Good Storage Practices for Pharmaceuticals, WHO, Canada GMP Guidelines 2009]
Retest Period
The period of time during which the drug substance is expected to remain within its specification and, therefore, can be used in the manufacture of a given drug product, provided that the drug substance has been stored under the defined conditions. After this period, a batch of drug substance destined for use in the manufacture of a drug product should be re-tested for compliance with the specification and then used immediately. A batch of drug substance can be re-tested multiple times and a different portion of the batch used after each re-test, as long as it continues to comply with the specification. For most biotechnological/biological substances known to be labile, it is more appropriate to establish a shelf life than a re-test period. The same may be true for certain antibiotics. [ICH Q1A]
The period of time during which a drug substance can be considered to remain within the specifications and therefore acceptable for use in the fabrication of a given drug product, provided that it has been stored under defined conditions, after this period, the batch is re-tested for compliance with specifications and then used immediately. [Canadian GMP Guidelines 2009]
Retrospective Validation
Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data. [EU GMP Guide, Annex 15, PIC/S PI 006-3]
Involves the evaluation of past experience of production on the condition that composition, procedures, and equipment remain unchanged. [Main Principles for Pharmaceutical Products, WHO]
Return
Sending back to the manufacturer or distributor of a medicinal product which may or may not present a quality defect. [EU GMP Guide, Glossary]
Revalidation
A repeat of the process validation to provide an assurance that changes in the process/equipment introduced in accordance with change control procedures do not adversely affect process characteristics and product quality. [EU GMP Guide, Annex15, PIC/S PI 006-3]
Repeated validation of an approved process (or a part thereof) to ensure continued compliance with established requirements. [Main Principles for Pharmaceutical Products, WHO]
Repetition of the validation process or a specific portion of it. [PIC/S PI 011-3]
Reversible Toxicity
The occurrence of harmful effects that are caused by a substance and which disappear after exposure to the substance ends. [ICH Q3C]
Rework
Action taken on a nonconforming product so that it will fulfill the specified DMR requirements before it is released for distribution. [21 CFR Part 820, FDA]
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). [EU GMP Guide, Part II, ICH Q7]
Subjecting an in-process drug, a bulk process intermediate (final biological bulk intermediate), or final product of a single batch/lot to an alternate manufacturing process due to a failure to meet predetermined specifications. Reworking is an unexpected occurrence and is not pre-approved as part of the marketing authorization. [Canadian GMP Guidelines 2009]
Risk
The combination of the probability of occurrence of harm and the severity of that harm. [ICH Q9, ISO/IEC Guide 51, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Acceptance
The decision to accept risk (ISO Guide 73). [ICH Q9]
Risk Analysis
Method to assess and characterise the critical parameters in the functionality of an equipment or process. [EU GMP Guide, Annex 15] The estimation of the risk associated with the identified hazards. [ICH Q9]
Risk Assessment
The systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards [ICH Q9, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Communication
The sharing of information about risk and risk management between the decision maker and other stakeholders. [ICH Q9]
Risk Control
Actions implementing risk management decisions (ISO Guide 73). [ICH Q9]
Risk Evaluation
The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk. [ICH Q9]
Risk Identification
The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description. [ICH Q9]
Risk Management
The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating, and reviewing risk. [ICH Q9, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Management Plan
A detailed description of the risk management system. [Directive 2001/83/EC]
Risk Management System
A set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including the assessment of the effectiveness of those activities and interventions. [Directive 2001/83/EC]
Risk Priority Number (RPN)
A numeric assessment of risk assigned to a process, or steps in a process, as part of failure mode effects analysis (FMEA). Each failure mode gets a numeric score that quantifies likelihood of occurrence, likelihood of detection and severity of impact. The product of these three scores is the RPN for that failure mode. RPN = severity rating × occurrence rating × detection rating. [TRS 981 Annex 2, WHO]
Risk Reduction
Actions taken to lessen the probability of occurrence of harm and the severity of that harm. [ICH Q9]
Risk Review
Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. [ICH Q9]
Risk-benefit Balance
An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks as defined in point 28, first indent. [Directive 2001/83/EC]
Robustness
The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. [ICH Q2]
A composite (solid, liquid, gaseous, or in solution) of equimolar quantities of two enantiomeric species. It is devoid of optical activity. [ICH Q6A]
Radio Synthesizer Unit (RSU)
A closed-system device for the synthesis of radioactive drug substances used in the manufacturing of PERs. The system may be controlled by graphical computer software programs. [Canadian GMP Guidelines, Annex 5]
Radioactive Concentration
Amount of radioactivity per unit volume such as mCi/ml or MBq/ml. [Canadian GMP Guidelines, Annex 3, Annex 5]
Radioactivity
Spontaneous decay of unstable nuclei and is quantified as the number of disintegrations per unit of time as given in Becquerel (Bq) or Curie (Ci) units. [Canadian GMP Guidelines, Annex 3, Annex 5]
Radionuclide
A nuclide with an unstable or excited nucleus (imbalance of protons and neutrons) which will undergo spontaneous transformation with emissions of subatomic particles and/or photons of energy. [Canadian GMP Guidelines, Annex 3]
Radionuclide Generator
Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be obtained by elution or by any other method used in a radiopharmaceutical. [Directive 2001/83/EC]
Radionuclide PrecursorAny other radionuclide produced for the radio-labelling of another substance prior to administration. [Directive 2001/83/EC]
Radiopharmaceutical
Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [EU GMP Guide, Glossary, Directive 2001/83/EC]
Random Sample
Sample in which the different fractions of the material have an equal probability of being represented. [Sampling Operations, WHO]
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. [EU GMP Guide, Annex13, Canadian GMP Guidelines, Annex 13]
Randomisation Code
A listing in which the treatment assigned to each subject from the randomisation process is identified. [EU GMP Guide, Annex 13, Canadian GMP Guidelines 2009, Annex 13]
Range
The range of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. [ICH Q2]
Rapidly Dissolving Product
An immediate release solid oral drug product is considered rapidly dissolving when not less than 80% of the label amount of the drug substance dissolves within 15 minutes in each of the following media: (1) pH 1.2, (2) pH 4.0, and (3) pH 6.8. [ICH Q6A]
Raw Data
Any work-sheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities and which are necessary for the reconstruction and evaluation of a work project, process or study report, etc. Raw data may be hard/paper copy or electronic but must be known and defined in system procedures. [PIC/S PI 011-3]
Raw Material
A general term used to denote starting materials, reagents, and solvents intended for use in the production of intermediates or APIs. [EU GMP Guide, Part II, ICH Q7]
Any substance, other than in-process drug or packaging material, intended to be used in the manufacture of drugs, including those that appear in the master formula but that do not appear in the drug such as solvents and processing aids. [Canadian GMP Guidelines 2009]
Reagent
A substance other than a starting material, intermediate, or solvent that is used in the manufacture of a new drug substance. [ICH Q6A, Q3A]
Real-Time Release Testing (RTRT)
The ability to evaluate and ensure the quality of in-process and/or final product based on process data, which typically include a valid combination of measured material attributes and process controls. [ICH Q8]
Receiving Unit (RU)The involved disciplines at an organization where a designated product, process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Reconciliation
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically and actually produced or used. [EU GMP Guide, Glossary]
A comparison between the theoretical quantity and the actual quantity. [Main Principles for Pharmaceutical Products, WHO]
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically produced or used and the amount actually produced or used. [Canadian GMP Guidelines 2009]
Recovered Plasma
The liquid portion of a single donation of whole blood separated from cellular components and intended for further manufacture. [Canadian GMP Guidelines, Annex 14]
Recovery
The introduction of all or part of previous batches (or of redistilled solvents and similar products) of the required quality into another batch at a defined stage of manufacture. It includes the removal of impurities from waste to obtain a pure substance or the recovery of used materials for a separate use. [EU GMP Guide, Glossary, Main Principles for Pharmaceutical Products, WHO, Canadian GMP Guidelines 2009]
Reference Sample (see also Retention Sample)
Sample of a batch of starting material, packaging material or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned. Where stability permits, reference samples from critical intermediate stages (e.g. those requiring analytical testing and release) or intermediates, that are transported outside of the manufacturer’s control, should be kept. [EU GMP Guide, Annex 19]
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. [EU GMP Guide, Part II, ICH Q7]
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. [EU GMP Guide, Part II, ICH Q7]
Regulated User
The regulated Good Practice entity, that is responsible for the operation of a computerised system and the applications, files and data held thereon. [PIC/S PI 011-3]
Regulatory Authority
A government agency or other entity in an MRA country that has a legal right to control the use or sale of drugs within that country and that may take enforcement action to ensure that drugs marketed within its jurisdiction comply with legal requirements. [Canadian GMP Guidelines 2009]
Relative Humidity
The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of the air at the same temperature expressed as a percentage. More simply put, it is the ratio of the mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given temperature. [Main Principles for Pharmaceutical Products, WHO]
Releasing Officer
The person who releases the prepared medicinal products. This person may be the Responsible Person. [PIC/S PE 010-4]
Relevant Genotypic and Phenotypic Marker
Those markers permitting the identification of the strain of the cell line which should include the expression of the recombinant protein or presence of the expression construct. [ICH Q5B]
Relevant Virus
Virus used in process evaluation studies which is either the identified virus, or of the same species as the virus that is known, or likely to contaminate the cell substrate or any other reagents or materials used in the production process. [ICH Q5A]
Remanufacturer
Any person who processes, conditions, renovates, repackages, restores, or does any other act to a finished [medical] device that significantly changes the finished device‘s performance or safety specifications, or intended use. [21 CFR Part 820, FDA]
Repeatability
Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision. [ICH Q2]
Reporting ThresholdA limit above (>) which an impurity should be reported. Reporting threshold is the same as reporting level in Q2B. [ICH Q3A]
A limit above (>) which a degradation product should be reported. [ICH Q3B]
Representative Sample
Sample obtained according to a sampling procedure designed to ensure that the different parts of a batch or the different properties of a non-uniform material are proportionately represented. [Sampling Operations, WHO]
A sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled. [21 CFR Part 210, FDA]
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. [EU GMP Guide, Glossary]
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. [EU GMP Guide, Part II, ICH Q7]
Subjecting all or part of a batch or lot of an in-process drug, bulk process intermediate (final biological bulk intermediate) or bulk product of a single batch/ lot to a previous step in the validated manufacturing process due to failure to meet predetermined specifications. Reprocessing procedures are foreseen as occasionally necessary for biological drugs and, in such cases, are validated and pre-approved as part of the marketing authorization. [Main Principles for Pharmaceutical Products, WHO, Canadian GMP Guidelines 2009]
Reproducibility
Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology). [ICH Q2]
Requirement
The explicit or implicit needs or expectations of the patients or their surrogates (e.g., health care professionals, regulators and legislators). In this document, “requirements” refers not only to statutory, legislative, or regulatory requirements, but also to such needs and expectations. [ICH Q9]
Responsible Person
The person who is ultimately responsible for all aspects of the preparation of medicinal products including the release of these items. This person must have sufficient scientific and technical education and experience to perform this duty. [PICS/S PE 010-4]
Retention Sample (see also Reference Sample)
A sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes. For example, presentation, packaging, labelling, patient information leaflet, batch number, expiry date should the need arise during the shelf life of the batch concerned. There may be exceptional circumstances where this requirement can be met without retention of duplicate samples e.g. where small amounts of a batch are packaged for different markets or in the production of very expensive medicinal products. For finished products, in many instances the reference and retention samples will be presented identically, i.e. as fully packaged units. In such circumstances, reference and retention samples may be regarded as interchangeable [EU GMP Guide, Annex 19]
Sample collected as part of the original sampling process and reserved for future testing. The size of a retention sample should be sufficient to allow for at least two confirmatory analyses. In some cases statutory regulations may require one or more retention samples, each of which should be separately identified, packaged and sealed. [Sampling Operations, WHO]
Retest Date
The date after which samples of the drug substance should be examined to ensure that the material is still in compliance with the specification and thus suitable for use in the manufacture of a given drug product. [ICH Q1A]
The date when a material should be re-examined to ensure that it is still suitable for use. [ICH Q7]
The date when a material should be re-examined to ensure that it is still suitable for use. [EU GMP Guide, Part II, Guide to Good Storage Practices for Pharmaceuticals, WHO, Canada GMP Guidelines 2009]
Retest Period
The period of time during which the drug substance is expected to remain within its specification and, therefore, can be used in the manufacture of a given drug product, provided that the drug substance has been stored under the defined conditions. After this period, a batch of drug substance destined for use in the manufacture of a drug product should be re-tested for compliance with the specification and then used immediately. A batch of drug substance can be re-tested multiple times and a different portion of the batch used after each re-test, as long as it continues to comply with the specification. For most biotechnological/biological substances known to be labile, it is more appropriate to establish a shelf life than a re-test period. The same may be true for certain antibiotics. [ICH Q1A]
The period of time during which a drug substance can be considered to remain within the specifications and therefore acceptable for use in the fabrication of a given drug product, provided that it has been stored under defined conditions, after this period, the batch is re-tested for compliance with specifications and then used immediately. [Canadian GMP Guidelines 2009]
Retrospective Validation
Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data. [EU GMP Guide, Annex 15, PIC/S PI 006-3]
Involves the evaluation of past experience of production on the condition that composition, procedures, and equipment remain unchanged. [Main Principles for Pharmaceutical Products, WHO]
Return
Sending back to the manufacturer or distributor of a medicinal product which may or may not present a quality defect. [EU GMP Guide, Glossary]
Revalidation
A repeat of the process validation to provide an assurance that changes in the process/equipment introduced in accordance with change control procedures do not adversely affect process characteristics and product quality. [EU GMP Guide, Annex15, PIC/S PI 006-3]
Repeated validation of an approved process (or a part thereof) to ensure continued compliance with established requirements. [Main Principles for Pharmaceutical Products, WHO]
Repetition of the validation process or a specific portion of it. [PIC/S PI 011-3]
Reversible Toxicity
The occurrence of harmful effects that are caused by a substance and which disappear after exposure to the substance ends. [ICH Q3C]
Rework
Action taken on a nonconforming product so that it will fulfill the specified DMR requirements before it is released for distribution. [21 CFR Part 820, FDA]
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). [EU GMP Guide, Part II, ICH Q7]
Subjecting an in-process drug, a bulk process intermediate (final biological bulk intermediate), or final product of a single batch/lot to an alternate manufacturing process due to a failure to meet predetermined specifications. Reworking is an unexpected occurrence and is not pre-approved as part of the marketing authorization. [Canadian GMP Guidelines 2009]
Risk
The combination of the probability of occurrence of harm and the severity of that harm. [ICH Q9, ISO/IEC Guide 51, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Acceptance
The decision to accept risk (ISO Guide 73). [ICH Q9]
Risk Analysis
Method to assess and characterise the critical parameters in the functionality of an equipment or process. [EU GMP Guide, Annex 15] The estimation of the risk associated with the identified hazards. [ICH Q9]
Risk Assessment
The systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards [ICH Q9, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Communication
The sharing of information about risk and risk management between the decision maker and other stakeholders. [ICH Q9]
Risk Control
Actions implementing risk management decisions (ISO Guide 73). [ICH Q9]
Risk Evaluation
The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk. [ICH Q9]
Risk Identification
The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description. [ICH Q9]
Risk Management
The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating, and reviewing risk. [ICH Q9, Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Risk Management Plan
A detailed description of the risk management system. [Directive 2001/83/EC]
Risk Management System
A set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including the assessment of the effectiveness of those activities and interventions. [Directive 2001/83/EC]
Risk Priority Number (RPN)
A numeric assessment of risk assigned to a process, or steps in a process, as part of failure mode effects analysis (FMEA). Each failure mode gets a numeric score that quantifies likelihood of occurrence, likelihood of detection and severity of impact. The product of these three scores is the RPN for that failure mode. RPN = severity rating × occurrence rating × detection rating. [TRS 981 Annex 2, WHO]
Risk Reduction
Actions taken to lessen the probability of occurrence of harm and the severity of that harm. [ICH Q9]
Risk Review
Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. [ICH Q9]
Risk-benefit Balance
An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks as defined in point 28, first indent. [Directive 2001/83/EC]
Robustness
The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. [ICH Q2]