S
Safety Study
Any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures. [Directive 2001/83/EC]
Sample
A portion of a material collected according to a defined sampling procedure. The size of any sample should be sufficient to allow all anticipated test procedures to be carried out, including all repetitions and retention samples. If the quantity of material available is not sufficient for the intended analyses and for the retention samples, the inspector should record that the sampled material is the available sample (see Sampling record) and the evaluation of the results should take account of the limitations that arise from the insufficient sample size. [Sampling Operations, WHO]
Sampler
Person responsible for performing the sampling operations. [Sampling Operations, WHO]
Sampling
Operations designed to obtain a representative portion of a pharmaceutical product, based on an appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments or batch release. [Good Distribution Practices for Pharmaceutical Products, WHO]
Sampling Frequency
Established period for collecting samples. [PIC/S PI 007-6]
Sampling Method
That part of the sampling procedure dealing with the method prescribed for withdrawing samples. [Sampling Operations, WHO]
Sampling Plan
Description of the location, number of units and/or quantity of material that should be collected, and associated acceptance criteria. [Sampling Operations, WHO]
Sampling Procedure
The complete sampling operations to be performed on a defined material for a specific purpose. A detailed written description of the sampling procedure is provided in the sampling protocol. [Sampling Operations, WHO]
Sampling Record
Written record of the sampling operations carried out on a particular material for a defined purpose. The sampling record should contain the batch number, date and place of sampling, reference to the sampling protocol used, a description of the containers and of the materials sampled, notes on possible abnormalities, together with any other relevant observations, and the name and signature of the inspector. [Sampling Operations, WHO]
Sampling Unit
Discrete part of a consignment such as an individual package, drum or container. [Sampling Operations, WHO]
Scaffold
A support, delivery vehicle or matrix that may provided structure for or facilitate the migration, binding or transport of cells and/or bioactive molecules. [EU GMP Guide, Annex 2]
Scale Up
Increase in the production scale, for example, from pilot plant to production plant. [Canadian GMP Guidelines, Annex 2]
Steps in the fermentation process whereby the production cell line/seed line is expanded until it reaches a sufficient concentration for seeding the seed and/or production bioreactors. [Canadian GMP Guidelines, Annex 2]
Seed Lot
Seed lot system: A seed lot system is a system according to which successive batches of a product are derived from the same master seed lot at a given passage level. For routine production, a working seed lot is prepared from the master seed lot. The final product is derived from the working seed lot and has not undergone more passages from the master seed lot than the vaccine shown in clinical studies to be satisfactory with respect to safety and efficacy. The origin and the passage history of the master seed lot and the working seed lot are recorded. Master seed lot: A culture of a micro-organism distributed from a single bulk into containers in a single operation in such a manner as to ensure uniformity, to prevent contamination and to ensure stability. A master seed lot in liquid form is usually stored at or below –70 °C. A freeze-dried master seed lot is stored at a temperature known to ensure stability. Working seed lot: A culture of a micro-organism derived from the master seed lot and intended for use in production. Working seed lots are distributed into containers and stored as described above for master seed lots. [EU GMP Guide, Glossary]
Collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. In contrast to cell bank, seed lot may describe collections of plasmids, viruses etc. For master and working seed lots, refer to definitions provided for MCB and WCB. [Canadian GMP Guidelines 2009, Annex 2]
Selected Sample
Sample obtained according to a sampling procedure designed to select a fraction of the material that is likely to have special properties. A selected sample that is likely to contain deteriorated, contaminated, adulterated or otherwise unacceptable material is known as an extreme sample. [Sampling Operations, WHO]
Self Audit
An assessment, undertaken under the responsibility of the same organisation in order to monitor the validity of the quality assurance system and the compliance with this guide. It can be conducted by designated competent person(s) from the organisation or assisted by external experts. [PIC/S PE 010-4]
Self-contained Area
Premises which provide complete and total separation of all aspects of an operation, including personnel and equipment movement, with well established procedures, controls and monitoring. This includes physical barriers as well as separate air-handling systems, but does not necessarily imply two distinct and separate buildings. [Main Principles for Pharmaceutical Products, WHO]
Self-contained Facility(installation confinée) Means a premise that provides complete and total separation of all aspects of the operation, including personnel and equipment movement, with well established procedures, controls and monitoring. This includes physical barriers and separate utilities such as air handling systems. A self-contained facility does not necessarily imply a distinct and separate building. [Canadian GMP Guidelines 2009]
Semipermeable Container
Containers that allow the passage of solvent, usually water, while preventing solute loss. The mechanism for solvent transport occurs by absorption into one container surface, diffusion through the bulk of the container material, and desorption from the other surface. Transport is driven by a partial-pressure gradient. Examples of semi-permeable containers include plastic bags and semi-rigid, low-density polyethylene (LDPE) pouches for large volume parenterals (LVPs), and LDPE ampoules, bottles, and vials. [ICH Q1A]
Sending Unit (SU)The involved disciplines at an organization from where a designated product, process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Senior ManagementTop management officials in a firm who have the authority and responsibility to mobilize resources. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Person(s) who direct and control a company or site at the highest levels with the authority and responsibility to mobilise resources within the company or site. [ICH Q10]
SensitivityCapacity of the test procedure to record small variations in concentration of a component, with a defined degree of precision. [PIC/S PI 006-3]
Serious Adverse Event (SAE)(see also Adverse Event)
Any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or in a congenital anomaly or birth defect. [Directive 2001/20/EC]
Serious Adverse Reaction (SAR)(see also Adverse Reaction)
An adverse reaction which results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect. [Directive 2001/83/EC]
Serum
The liquid portion of clotted blood. [Canadian GMP Guidelines, Annex 14]
Service Level Agreement (SLA)
A service level agreement or contract is a negotiated agreement between the customer and service provider that defines the common understanding about materials or service quality specifications, responsibilities, guarantees and communication mechanisms. It can either be legally binding, or an information agreement. The SLA may also specify the target and minimum level performance, operation or other service attributes. [TRS 961 Annex 9, WHO]
SeverityA measure of the possible consequences of a hazard. [ICH Q9]
Shelf Life SpecificationThe combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life. [ICH Q1A]
Shelf-Life(see also Expiry Date) he time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label. [ICH Q1A]
The period of time during which a pharmaceutical product, if stored correctly, is expected to comply with the specification as determined by stability studies on a number of batches of the product. The shelf-life is used to establish the expiry date of each batch. [Good Distribution Practices for Pharmaceutical Products, WHO]
(durée de conservation) The time interval during which a drug product is expected to remain within the approved specification provided that it is stored under the conditions defined on the label and in the proposed containers and closure. [Canadian GMP Guidelines 2009]
ShiftScheduled periods of work or production, usually less than 12 hours in length, staffed by alternating groups of workers. [PIC/S PI 007-6]
Shipping
The operation of packaging for shipment and sending of ordered medicinal products for clinical trials. [EU GMP Guide, Annex 13, Canadian GMP Guidelines, Annex 13]
Shipping (or dispatch) is the assembly, packing for shipment, and sending of ordered medicinal products for clinical trials. [Specific Pharmaceutical Products, WHO]
Signed / Signature
The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature. [EU GMP Guide, Part II, ICH Q7]
Simulated Product
A material that closely approximates the physical and, where practical, the chemical characteristics (e.g. viscosity, particle size, pH etc.) of the product under validation. In many cases, these characteristics may be satisfied by a placebo product batch. [EU GMP Guide, Annex 15, PIC/S PI 006-3]
Site Acceptance Test (SAT)
Final acceptance of an equipment or system by the customer, performed at the site where the equipment/system will be operated.
Solvent
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API. [EU GMP Guide, Part II, ICH Q7]
An inorganic or an organic liquid used as a vehicle for the preparation of solutions or suspensions in the synthesis of a new drug substance or the manufacture of a new drug product. [ICH Q3A, Q6A]
Somatic Cell
Cells, other than reproductive (germ line) cells, which make up the body of a human or animal. These cells may be autologous (from the patient), allogeneic (from another human being) or xenogeneic (from animals) somatic living cells, that have been manipulated or altered ex vivo, to be administered in humans to obtain a therapeutic, diagnostic or preventive effects. [EU GMP Guide, Annex 2]
Source Code
An original computer program expressed in human-readable form (programming language), which must be translated into machine-readable form before it can be executed by the computer. [PIC/S PI 011-3]
Source Plasma
Plasma collected by plasmapheresis and used for further manufacture. [Canadian GMP Guidelines, Annex 14]
Specific Activity
Amount of radioactivity per unit mass or per mole such as mCi/mg, MBq/mg or mCi/mole, MBq/mole. [Canadian GMP Guidelines, Annex 3, Annex 5]
Specific Model Virus
Virus which is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties to those of the observed or suspected virus. [ICH Q5A]
Specific Test
A test which is considered to be applicable to particular new drug substances or particular new drug products depending on their specific properties and/or intended use. [ICH Q6A]
Specification
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. "Conformance to specification" means that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria. [EU GMP Guide, Part II, ICH Q7, ICH Q6A, Q6B, Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA]
A list of detailed requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. [Main Principles for Pharmaceutical Products, WHO]
Any requirement with which a product, process, service, or other activity must conform. [21 CFR Part 820, FDA]
Means a detailed description of a drug, the raw material used in a drug, or the packaging material for a drug and includes:
Specification (Release)
The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug product at the time of its release. [ICH Q1A]
Specification (Shelf Life)
The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life. [ICH Q1A]
Specificity
The ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). [ICH Q2]
Specified Degradation Product
A degradation product that is individually listed and limited with a specific acceptance criterion in the new drug product specification. A specified degradation product can be either identified or unidentified. [ICH Q3B]
Specified Impurity
An impurity that is individually listed and limited with a specific acceptance criterion in the new drug substance specification. A specified impurity can be either identified or unidentified. [ICH Q3A]
An identified or unidentified impurity that is selected for inclusion in the new drug substance or new drug product specification and is individually listed and limited in order to assure the quality of the new drug substance or new drug product. [ICH Q6A]
SpikingThe addition of a known amount of a compound to a standard, sample or placebo, typically for the purpose of confirming the performance of an analytical procedure. [TRS 961 Annex 7, WHO]
Sponsor
An individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial. [EU GMP Guide, Annex 13]
A person who takes responsibility for and initiates a clinical investigation. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
An individual, company, institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial. When an investigator independently initiates and takes full responsibility for a trial, the investigator then also assumes the role of the sponsor. [Specific Pharmaceutical Products, WHO]
An individual, corporate body, institution or organization that conducts a clinical trial. [Canadian GMP Guidelines 2009, Annex 13]
Sporicidal Process
A gaseous, vapour or liquid treatment applied to surfaces, using an agent that is recognised as capable of killing bacterial and fungal spores. The process is normally validated using biological indicators containing bacterial spores. The number of spore log reductions is not specified in this definition, but a target of six log reductions is often applied. The process is applied to internal surfaces of the isolator and external surfaces of materials inside the isolator, when conventional sterilization methods are not required. The application of a sporicidal process to isolators is not considered to be a sterilization process in the same way as, for example, a sealed container subjected to a validated dry heat, moist heat or irradiation process. [PIC/S PI 014-3]
Stakeholder
Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority, and industry. [ICH Q9]
An individual or organization having an ownership or interest in the delivery, results, and metrics of the quality system framework or business process improvements. [Guidance for Industry: Quality Systems Approach for Pharmaceutical cGMP Regulations, FDA]
Standalone System
A self-contained computer system, which provides data processing, monitoring or control functions but which is not embedded within automated equipment. This is contrasted with an embedded system, the sole purpose of which is to control a particular piece of automated equipment. [PIC/S PI 011-3]
Standard Operating Procedure (SOP)
An authorized, written procedure giving instructions for performing operations not necessarily specific to a given product or material, but of a more general nature (e.g. equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control, sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documentation. [WHO: TRS 961 Annex 7, Inspection, Main Principles for Pharmaceutical Products, Good Distribution Practices for Pharmaceutical Products]
A written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (e.g., equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control, sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documents. [Canadian GMP Guidelines 2009]
Starting Material
Any substance used in the production of a medicinal product, but excluding packaging materials. [EU GMP Guide, Glossary, PIC/S PE 010-4]
A material used in the synthesis of a new drug substance that is incorporated as an element into the structure of an intermediate and/or of the new drug substance. Starting materials are normally commercially available and of defined chemical and physical properties and structure. [ICH Q3A]
Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials. [Main Principles for Pharmaceutical Products, WHO]
(produit de depart) Any substance entering a production facility for use in the production of a drug product. [Canadian GMP Guidelines, Annex 5]
All biological and chemical materials used in the manufacture of biological products, excluding excipient. [Chinese GMP Guidelines, Annex 3]
Stasis Test
Also referred to as an inhibition test, which is performed to ensure that there are no inhibitory substances remaining in the product and that the media is still capable of supporting the growth of micro-organisms at the end of the sterility test incubation period. This test is not mandatory but it may be useful to confirm the inactivation of antimicrobial substances in products where a marginal test methodology is employed routinely, after an initial successful test validation. [PIC/S PI 012-3]
State of Control
A condition in which the set of controls consistently provides assurance of continued process performance and product quality. [EU GMP Guide, Annex 15, ICH Q10]
Sterile
Free of any viable organisms. (In practice, no such absolute statement regarding the absence of microorganisms can be proven, see sterilisation.). [PIC/S PI 007-6]
Free from viable microorganisms. [Canadian GMP Guidelines 2009]
Sterile Product
For purposes of this guidance, sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Sterility
Sterility is the absence of living organisms. The conditions of the sterility test are given in the European Pharmacopoeia. [EU GMP Guide, Glossary]
Sterility Assurance Level (SAL)
Probability that a batch of product is sterile. (SAL is expressed as 10 -n). [PIC/S PI 007-6]
Sterility Assurance System
The sum total of the arrangements made to assure the sterility of products. For terminally sterilized products these typically include the following stages:
(a) Product design
(b) Knowledge of and, if possible, control of the microbiological condition of starting materials and process aids ( e.g. gases and lubricants).
(c) Control of the contamination of the process of manufacture to avoid the ingress of microorganisms and their multiplication in the product. This is usually accomplished by cleaning and sanitization of product contact surfaces, prevention of aerial contamination by handling in clean rooms, use of process control time limits and, if applicable, filtration stages.
(d) Prevention of mix up between sterile and non sterile product streams.
(e) Maintenance of product integrity.
(f) The sterilization process.
(g) The totality of the Quality System that contains the Sterility Assurance System e.g. change control, training, written procedures, release checks, planned preventative maintenance, failure mode analysis, prevention of human error, validation calibration, etc. [EU GMP Guide, Annex17]
Sterility Test
Test performed to determine if viable microorganisms are present. [PIC/S PI 007-6]
Sterilization
Validated process used to render a product free of viable organisms. Note: In a sterilization process, the nature of microbiological death of reduction is described by an exponential function. Therefore, the number of microorganisms which survive a sterilization process can be expressed in terms of probability. While the probability may be reduced to a very low number, it can never be reduced to zero. [PIC/S PI 007-6]
Sterilizing Filter
A filter used to render a material sterile. Sterilizing filters have a rated pore size of 0.2 µm or less. [Canadian GMP Guidelines 2009]
Sterilizing Grade Filter
A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Stock Preparation
A product, which is prepared for stock and is available for dispensing. [PIC/S PE 010-4]
Storage
The storing of pharmaceutical products and materials up to their point of use. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Storage Condition Tolerance
The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage condition within the ranges defined in this guideline. The actual temperature and humidity (when controlled) should be monitored during stability storage. Short term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed, and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed. [ICH Q1A]
Strength
The concentration of the drug substance (for example, weight/ weight, weight/volume, or unit dose/volume basis), and/or
Stress Testing (drug product)
Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photostability testing (see ICH Q1B) and specific testing on certain products, (e.g., metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products). [ICH Q1A]
Stress Testing (drug substance)
Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing. [ICH Q1A]
Strongly Suspected Human Carcinogen
A substance for which there is no epidemiological evidence of carcinogenesis but there are positive genotoxicity data and clear evidence of carcinogenesis in rodents. [ICH Q3C]
Structural Integrity (software)
Software attributes reflecting the degree to which source code satisfies specified software requirements and conforms to contemporary software development practices and standards. [PIC/S PI 011-3]
Structural Testing
Examining the internal structure of the source code. Includes low-level and high-level code review, path analysis, auditing of programming procedures and standards actually used, inspection for extraneous “dead code”, boundary analysis and other techniques. Requires specific computer science and programming expertise. [PIC/S PI 011-3]
Structural VerificationAn activity intended to produce documented assurance that software has appropriate structural integrity. [PIC/S PI 011-3]
Subculture
Splitting of a cell population by a defined procedure to reduce the cell concentration or density and make possible cell expansion. [Canadian GMP Guidelines, Annex 2]
Suite
Functional manufacturing area consisting of one or more rooms with shared air handling and personnel access and which is segregated from the rest of the facility. It contains a separate air supply and exhaust, separate personnel access/egress and separate process equipment. It does not necessarily include a separate supply of water, compressed air/gas or steam, provided that suitable engineering controls are in place to prevent product contamination of these systems. A suite is referred to as a facility within a facility. [Canadian GMP Guidelines, Annex 2]
Supplier
A person providing pharmaceutical products and materials on request. Suppliers may be agents, brokers, distributors, manufacturers or traders. Where possible, suppliers should be authorized by a competent authority. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Supplying
All activities of providing, selling, donating medicinal products to wholesalers, pharmacists, or persons authorised or entitled to supply medicinal products to the public. [EU GDP Guidelines]
Supporting Data
Data, other than those from formal stability studies, that support the analytical procedures, the proposed re-test period or shelf life, and the label storage statements. Such data include
System
A group of equipment with a common purpose. [EU GMP Guide, Annex 15]
A regulated pattern of interacting activities and techniques which are united to form an organised whole. [EU GMP Guide, Glossary, Canadian GMP Guidelines 2009]
System Acceptance Test Specification
The system acceptance test specification is a description of those tests to be carried out to permit acceptance of the system by the user. Typically it should address the following:
System Software
Software designed to facilitate the operation and maintenance of a computer system and its associated programs, such as operating systems, assemblers, utilities, network software and executive programs. System software is generally independent of the specific application. [PIC/S PI 011-3]
System Specification
Describe how the system will meet the functional requirements. [PIC/S PI 011-3]
Any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures. [Directive 2001/83/EC]
Sample
A portion of a material collected according to a defined sampling procedure. The size of any sample should be sufficient to allow all anticipated test procedures to be carried out, including all repetitions and retention samples. If the quantity of material available is not sufficient for the intended analyses and for the retention samples, the inspector should record that the sampled material is the available sample (see Sampling record) and the evaluation of the results should take account of the limitations that arise from the insufficient sample size. [Sampling Operations, WHO]
Sampler
Person responsible for performing the sampling operations. [Sampling Operations, WHO]
Sampling
Operations designed to obtain a representative portion of a pharmaceutical product, based on an appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments or batch release. [Good Distribution Practices for Pharmaceutical Products, WHO]
Sampling Frequency
Established period for collecting samples. [PIC/S PI 007-6]
Sampling Method
That part of the sampling procedure dealing with the method prescribed for withdrawing samples. [Sampling Operations, WHO]
Sampling Plan
Description of the location, number of units and/or quantity of material that should be collected, and associated acceptance criteria. [Sampling Operations, WHO]
Sampling Procedure
The complete sampling operations to be performed on a defined material for a specific purpose. A detailed written description of the sampling procedure is provided in the sampling protocol. [Sampling Operations, WHO]
Sampling Record
Written record of the sampling operations carried out on a particular material for a defined purpose. The sampling record should contain the batch number, date and place of sampling, reference to the sampling protocol used, a description of the containers and of the materials sampled, notes on possible abnormalities, together with any other relevant observations, and the name and signature of the inspector. [Sampling Operations, WHO]
Sampling Unit
Discrete part of a consignment such as an individual package, drum or container. [Sampling Operations, WHO]
Scaffold
A support, delivery vehicle or matrix that may provided structure for or facilitate the migration, binding or transport of cells and/or bioactive molecules. [EU GMP Guide, Annex 2]
Scale Up
Increase in the production scale, for example, from pilot plant to production plant. [Canadian GMP Guidelines, Annex 2]
Steps in the fermentation process whereby the production cell line/seed line is expanded until it reaches a sufficient concentration for seeding the seed and/or production bioreactors. [Canadian GMP Guidelines, Annex 2]
Seed Lot
Seed lot system: A seed lot system is a system according to which successive batches of a product are derived from the same master seed lot at a given passage level. For routine production, a working seed lot is prepared from the master seed lot. The final product is derived from the working seed lot and has not undergone more passages from the master seed lot than the vaccine shown in clinical studies to be satisfactory with respect to safety and efficacy. The origin and the passage history of the master seed lot and the working seed lot are recorded. Master seed lot: A culture of a micro-organism distributed from a single bulk into containers in a single operation in such a manner as to ensure uniformity, to prevent contamination and to ensure stability. A master seed lot in liquid form is usually stored at or below –70 °C. A freeze-dried master seed lot is stored at a temperature known to ensure stability. Working seed lot: A culture of a micro-organism derived from the master seed lot and intended for use in production. Working seed lots are distributed into containers and stored as described above for master seed lots. [EU GMP Guide, Glossary]
Collection of appropriate containers, whose contents are of uniform composition, stored under defined conditions. In contrast to cell bank, seed lot may describe collections of plasmids, viruses etc. For master and working seed lots, refer to definitions provided for MCB and WCB. [Canadian GMP Guidelines 2009, Annex 2]
Selected Sample
Sample obtained according to a sampling procedure designed to select a fraction of the material that is likely to have special properties. A selected sample that is likely to contain deteriorated, contaminated, adulterated or otherwise unacceptable material is known as an extreme sample. [Sampling Operations, WHO]
Self Audit
An assessment, undertaken under the responsibility of the same organisation in order to monitor the validity of the quality assurance system and the compliance with this guide. It can be conducted by designated competent person(s) from the organisation or assisted by external experts. [PIC/S PE 010-4]
Self-contained Area
Premises which provide complete and total separation of all aspects of an operation, including personnel and equipment movement, with well established procedures, controls and monitoring. This includes physical barriers as well as separate air-handling systems, but does not necessarily imply two distinct and separate buildings. [Main Principles for Pharmaceutical Products, WHO]
Self-contained Facility(installation confinée) Means a premise that provides complete and total separation of all aspects of the operation, including personnel and equipment movement, with well established procedures, controls and monitoring. This includes physical barriers and separate utilities such as air handling systems. A self-contained facility does not necessarily imply a distinct and separate building. [Canadian GMP Guidelines 2009]
Semipermeable Container
Containers that allow the passage of solvent, usually water, while preventing solute loss. The mechanism for solvent transport occurs by absorption into one container surface, diffusion through the bulk of the container material, and desorption from the other surface. Transport is driven by a partial-pressure gradient. Examples of semi-permeable containers include plastic bags and semi-rigid, low-density polyethylene (LDPE) pouches for large volume parenterals (LVPs), and LDPE ampoules, bottles, and vials. [ICH Q1A]
Sending Unit (SU)The involved disciplines at an organization from where a designated product, process or method is expected to be transferred. [TRS 961 Annex 7, WHO]
Senior ManagementTop management officials in a firm who have the authority and responsibility to mobilize resources. [Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, FDA]
Person(s) who direct and control a company or site at the highest levels with the authority and responsibility to mobilise resources within the company or site. [ICH Q10]
SensitivityCapacity of the test procedure to record small variations in concentration of a component, with a defined degree of precision. [PIC/S PI 006-3]
Serious Adverse Event (SAE)(see also Adverse Event)
Any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or in a congenital anomaly or birth defect. [Directive 2001/20/EC]
Serious Adverse Reaction (SAR)(see also Adverse Reaction)
An adverse reaction which results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect. [Directive 2001/83/EC]
Serum
The liquid portion of clotted blood. [Canadian GMP Guidelines, Annex 14]
Service Level Agreement (SLA)
A service level agreement or contract is a negotiated agreement between the customer and service provider that defines the common understanding about materials or service quality specifications, responsibilities, guarantees and communication mechanisms. It can either be legally binding, or an information agreement. The SLA may also specify the target and minimum level performance, operation or other service attributes. [TRS 961 Annex 9, WHO]
SeverityA measure of the possible consequences of a hazard. [ICH Q9]
Shelf Life SpecificationThe combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life. [ICH Q1A]
Shelf-Life(see also Expiry Date) he time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label. [ICH Q1A]
The period of time during which a pharmaceutical product, if stored correctly, is expected to comply with the specification as determined by stability studies on a number of batches of the product. The shelf-life is used to establish the expiry date of each batch. [Good Distribution Practices for Pharmaceutical Products, WHO]
(durée de conservation) The time interval during which a drug product is expected to remain within the approved specification provided that it is stored under the conditions defined on the label and in the proposed containers and closure. [Canadian GMP Guidelines 2009]
ShiftScheduled periods of work or production, usually less than 12 hours in length, staffed by alternating groups of workers. [PIC/S PI 007-6]
Shipping
The operation of packaging for shipment and sending of ordered medicinal products for clinical trials. [EU GMP Guide, Annex 13, Canadian GMP Guidelines, Annex 13]
Shipping (or dispatch) is the assembly, packing for shipment, and sending of ordered medicinal products for clinical trials. [Specific Pharmaceutical Products, WHO]
Signed / Signature
The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature. [EU GMP Guide, Part II, ICH Q7]
Simulated Product
A material that closely approximates the physical and, where practical, the chemical characteristics (e.g. viscosity, particle size, pH etc.) of the product under validation. In many cases, these characteristics may be satisfied by a placebo product batch. [EU GMP Guide, Annex 15, PIC/S PI 006-3]
Site Acceptance Test (SAT)
Final acceptance of an equipment or system by the customer, performed at the site where the equipment/system will be operated.
Solvent
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API. [EU GMP Guide, Part II, ICH Q7]
An inorganic or an organic liquid used as a vehicle for the preparation of solutions or suspensions in the synthesis of a new drug substance or the manufacture of a new drug product. [ICH Q3A, Q6A]
Somatic Cell
Cells, other than reproductive (germ line) cells, which make up the body of a human or animal. These cells may be autologous (from the patient), allogeneic (from another human being) or xenogeneic (from animals) somatic living cells, that have been manipulated or altered ex vivo, to be administered in humans to obtain a therapeutic, diagnostic or preventive effects. [EU GMP Guide, Annex 2]
Source Code
An original computer program expressed in human-readable form (programming language), which must be translated into machine-readable form before it can be executed by the computer. [PIC/S PI 011-3]
Source Plasma
Plasma collected by plasmapheresis and used for further manufacture. [Canadian GMP Guidelines, Annex 14]
Specific Activity
Amount of radioactivity per unit mass or per mole such as mCi/mg, MBq/mg or mCi/mole, MBq/mole. [Canadian GMP Guidelines, Annex 3, Annex 5]
Specific Model Virus
Virus which is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties to those of the observed or suspected virus. [ICH Q5A]
Specific Test
A test which is considered to be applicable to particular new drug substances or particular new drug products depending on their specific properties and/or intended use. [ICH Q6A]
Specification
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. "Conformance to specification" means that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria. [EU GMP Guide, Part II, ICH Q7, ICH Q6A, Q6B, Guidance for Industry cGMP for Phase 1 Investigational Drugs, FDA]
A list of detailed requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. [Main Principles for Pharmaceutical Products, WHO]
Any requirement with which a product, process, service, or other activity must conform. [21 CFR Part 820, FDA]
Means a detailed description of a drug, the raw material used in a drug, or the packaging material for a drug and includes:
- a statement of all properties and qualities of the drug, raw material or packaging material that are relevant to the manufacture, packaging, and use of the drug, including the identity, potency, and purity of the drug, raw material, or packaging material,
- a detailed description of the methods used for testing and examining the drug, raw material, or packaging material, and
Specification (Release)
The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug product at the time of its release. [ICH Q1A]
Specification (Shelf Life)
The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life. [ICH Q1A]
Specificity
The ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). [ICH Q2]
Specified Degradation Product
A degradation product that is individually listed and limited with a specific acceptance criterion in the new drug product specification. A specified degradation product can be either identified or unidentified. [ICH Q3B]
Specified Impurity
An impurity that is individually listed and limited with a specific acceptance criterion in the new drug substance specification. A specified impurity can be either identified or unidentified. [ICH Q3A]
An identified or unidentified impurity that is selected for inclusion in the new drug substance or new drug product specification and is individually listed and limited in order to assure the quality of the new drug substance or new drug product. [ICH Q6A]
SpikingThe addition of a known amount of a compound to a standard, sample or placebo, typically for the purpose of confirming the performance of an analytical procedure. [TRS 961 Annex 7, WHO]
Sponsor
An individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial. [EU GMP Guide, Annex 13]
A person who takes responsibility for and initiates a clinical investigation. [Guidance for Industry: cGMP for Phase 1 Investigational Drugs, FDA]
An individual, company, institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial. When an investigator independently initiates and takes full responsibility for a trial, the investigator then also assumes the role of the sponsor. [Specific Pharmaceutical Products, WHO]
An individual, corporate body, institution or organization that conducts a clinical trial. [Canadian GMP Guidelines 2009, Annex 13]
Sporicidal Process
A gaseous, vapour or liquid treatment applied to surfaces, using an agent that is recognised as capable of killing bacterial and fungal spores. The process is normally validated using biological indicators containing bacterial spores. The number of spore log reductions is not specified in this definition, but a target of six log reductions is often applied. The process is applied to internal surfaces of the isolator and external surfaces of materials inside the isolator, when conventional sterilization methods are not required. The application of a sporicidal process to isolators is not considered to be a sterilization process in the same way as, for example, a sealed container subjected to a validated dry heat, moist heat or irradiation process. [PIC/S PI 014-3]
Stakeholder
Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority, and industry. [ICH Q9]
An individual or organization having an ownership or interest in the delivery, results, and metrics of the quality system framework or business process improvements. [Guidance for Industry: Quality Systems Approach for Pharmaceutical cGMP Regulations, FDA]
Standalone System
A self-contained computer system, which provides data processing, monitoring or control functions but which is not embedded within automated equipment. This is contrasted with an embedded system, the sole purpose of which is to control a particular piece of automated equipment. [PIC/S PI 011-3]
Standard Operating Procedure (SOP)
An authorized, written procedure giving instructions for performing operations not necessarily specific to a given product or material, but of a more general nature (e.g. equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control, sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documentation. [WHO: TRS 961 Annex 7, Inspection, Main Principles for Pharmaceutical Products, Good Distribution Practices for Pharmaceutical Products]
A written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (e.g., equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control, sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documents. [Canadian GMP Guidelines 2009]
Starting Material
Any substance used in the production of a medicinal product, but excluding packaging materials. [EU GMP Guide, Glossary, PIC/S PE 010-4]
A material used in the synthesis of a new drug substance that is incorporated as an element into the structure of an intermediate and/or of the new drug substance. Starting materials are normally commercially available and of defined chemical and physical properties and structure. [ICH Q3A]
Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials. [Main Principles for Pharmaceutical Products, WHO]
(produit de depart) Any substance entering a production facility for use in the production of a drug product. [Canadian GMP Guidelines, Annex 5]
All biological and chemical materials used in the manufacture of biological products, excluding excipient. [Chinese GMP Guidelines, Annex 3]
Stasis Test
Also referred to as an inhibition test, which is performed to ensure that there are no inhibitory substances remaining in the product and that the media is still capable of supporting the growth of micro-organisms at the end of the sterility test incubation period. This test is not mandatory but it may be useful to confirm the inactivation of antimicrobial substances in products where a marginal test methodology is employed routinely, after an initial successful test validation. [PIC/S PI 012-3]
State of Control
A condition in which the set of controls consistently provides assurance of continued process performance and product quality. [EU GMP Guide, Annex 15, ICH Q10]
Sterile
Free of any viable organisms. (In practice, no such absolute statement regarding the absence of microorganisms can be proven, see sterilisation.). [PIC/S PI 007-6]
Free from viable microorganisms. [Canadian GMP Guidelines 2009]
Sterile Product
For purposes of this guidance, sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Sterility
Sterility is the absence of living organisms. The conditions of the sterility test are given in the European Pharmacopoeia. [EU GMP Guide, Glossary]
Sterility Assurance Level (SAL)
Probability that a batch of product is sterile. (SAL is expressed as 10 -n). [PIC/S PI 007-6]
Sterility Assurance System
The sum total of the arrangements made to assure the sterility of products. For terminally sterilized products these typically include the following stages:
(a) Product design
(b) Knowledge of and, if possible, control of the microbiological condition of starting materials and process aids ( e.g. gases and lubricants).
(c) Control of the contamination of the process of manufacture to avoid the ingress of microorganisms and their multiplication in the product. This is usually accomplished by cleaning and sanitization of product contact surfaces, prevention of aerial contamination by handling in clean rooms, use of process control time limits and, if applicable, filtration stages.
(d) Prevention of mix up between sterile and non sterile product streams.
(e) Maintenance of product integrity.
(f) The sterilization process.
(g) The totality of the Quality System that contains the Sterility Assurance System e.g. change control, training, written procedures, release checks, planned preventative maintenance, failure mode analysis, prevention of human error, validation calibration, etc. [EU GMP Guide, Annex17]
Sterility Test
Test performed to determine if viable microorganisms are present. [PIC/S PI 007-6]
Sterilization
Validated process used to render a product free of viable organisms. Note: In a sterilization process, the nature of microbiological death of reduction is described by an exponential function. Therefore, the number of microorganisms which survive a sterilization process can be expressed in terms of probability. While the probability may be reduced to a very low number, it can never be reduced to zero. [PIC/S PI 007-6]
Sterilizing Filter
A filter used to render a material sterile. Sterilizing filters have a rated pore size of 0.2 µm or less. [Canadian GMP Guidelines 2009]
Sterilizing Grade Filter
A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent. [Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – cGMP, FDA]
Stock Preparation
A product, which is prepared for stock and is available for dispensing. [PIC/S PE 010-4]
Storage
The storing of pharmaceutical products and materials up to their point of use. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Storage Condition Tolerance
The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage condition within the ranges defined in this guideline. The actual temperature and humidity (when controlled) should be monitored during stability storage. Short term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed, and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed. [ICH Q1A]
Strength
The concentration of the drug substance (for example, weight/ weight, weight/volume, or unit dose/volume basis), and/or
- The potency, that is, the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (expressed, for example, in terms of units by reference to a standard). [21 CFR Part 210, FDA]
Stress Testing (drug product)
Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photostability testing (see ICH Q1B) and specific testing on certain products, (e.g., metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products). [ICH Q1A]
Stress Testing (drug substance)
Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing. [ICH Q1A]
Strongly Suspected Human Carcinogen
A substance for which there is no epidemiological evidence of carcinogenesis but there are positive genotoxicity data and clear evidence of carcinogenesis in rodents. [ICH Q3C]
Structural Integrity (software)
Software attributes reflecting the degree to which source code satisfies specified software requirements and conforms to contemporary software development practices and standards. [PIC/S PI 011-3]
Structural Testing
Examining the internal structure of the source code. Includes low-level and high-level code review, path analysis, auditing of programming procedures and standards actually used, inspection for extraneous “dead code”, boundary analysis and other techniques. Requires specific computer science and programming expertise. [PIC/S PI 011-3]
Structural VerificationAn activity intended to produce documented assurance that software has appropriate structural integrity. [PIC/S PI 011-3]
Subculture
Splitting of a cell population by a defined procedure to reduce the cell concentration or density and make possible cell expansion. [Canadian GMP Guidelines, Annex 2]
Suite
Functional manufacturing area consisting of one or more rooms with shared air handling and personnel access and which is segregated from the rest of the facility. It contains a separate air supply and exhaust, separate personnel access/egress and separate process equipment. It does not necessarily include a separate supply of water, compressed air/gas or steam, provided that suitable engineering controls are in place to prevent product contamination of these systems. A suite is referred to as a facility within a facility. [Canadian GMP Guidelines, Annex 2]
Supplier
A person providing pharmaceutical products and materials on request. Suppliers may be agents, brokers, distributors, manufacturers or traders. Where possible, suppliers should be authorized by a competent authority. [Guide to Good Storage Practices for Pharmaceuticals, WHO]
Supplying
All activities of providing, selling, donating medicinal products to wholesalers, pharmacists, or persons authorised or entitled to supply medicinal products to the public. [EU GDP Guidelines]
Supporting Data
Data, other than those from formal stability studies, that support the analytical procedures, the proposed re-test period or shelf life, and the label storage statements. Such data include
- stability data on early synthetic route batches of drug substance, small scale batches of materials, investigational formulations not proposed for marketing, related formulations, and product presented in containers and closures other than those proposed for marketing,
- information regarding test results on containers, and
- other scientific rationales.
[ICH Q1A]
System
A group of equipment with a common purpose. [EU GMP Guide, Annex 15]
A regulated pattern of interacting activities and techniques which are united to form an organised whole. [EU GMP Guide, Glossary, Canadian GMP Guidelines 2009]
System Acceptance Test Specification
The system acceptance test specification is a description of those tests to be carried out to permit acceptance of the system by the user. Typically it should address the following:
- System functionality
- System performance
- Critical parameters
- Operating procedures
System Software
Software designed to facilitate the operation and maintenance of a computer system and its associated programs, such as operating systems, assemblers, utilities, network software and executive programs. System software is generally independent of the specific application. [PIC/S PI 011-3]
System Specification
Describe how the system will meet the functional requirements. [PIC/S PI 011-3]