Glossary

Acceptable Exposure

Results of repeated environmental and/or biological monitoring studies showing no levels above established action levels.

Acceptance Criteria

Means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (of raw material, intermediate, packaging material, or active pharmaceutical ingredient) or any convenient subgroups of manufactured units. (Code of Fed. Regulations/CFR) This term can also be applied for validation.

Acceptable Ceiling Concentration

The maximum airborne concentration of a substance to which employees may be exposed at any time except for designated time periods during the concentration to which they are exposed must remain below the designated acceptable maximum level peak level for that substance.

Acceptable maximum Peak

The maximum airborne concentration of a substance to which employees may be exposed during excursions above an acceptable ceiling concentration.

Accuracy and precision (qualitative method)

In the context of the validation of a Rapid Microbiological Method accuracy and precision represents a direct method to show the equivalence of 2 qualitative methods. This is achieved by running them side by side and determining the degree to which the method under evaluation shows equivalence to the pharmacopoeial method. The accuracy and precision of the alternative method may be expressed as the relative rates of false positive and false negative results between the new method and the pharmacopoeial method using a standardized, low-level inoculums.

Accuracy (quantitative methods)

In the context of the validation of a quantitative Rapid Microbiological Method the accuracy is the closeness of the test results obtained by the alternative method to the value obtained by the pharmacopoeial method. Accuracy is usually expressed as the percentage of recovery of microorganisms by the method.

ACGIH

American Conference of Governmental Industrial Hygienists

Act

Means the Federal Food, Drug, and Cosmetic Act, as amended. (Code of Fed. Regulations/CFR)

Action Level

(1) In general, the level of a pollutant (contaminant) at which specified actions or counter measures are to be taken. (2) A term used by OSHA in several chemical standards. A level of exposure at which the employer must initiate some actions such as medical monitoring and training. The action level is generally set at 50% of the PEL. (3) This is the concentration or level of an agent at which it is deemed that some specific action should be taken. The action can range from more closely monitoring the exposure atmosphere to making engineering adjustments. In general practice the action level is usually set at one-half of the ACGIH TLV.

Action Limit

The action limit is reached when the acceptance criteria of a critical parameter have been exceeded. Results outside these limits will require specified action and investigation. (WHO GMP)

Active Pharmaceutical Ingredient (API)

A substance or compound that is intended to be used in the manufacture of a pharmaceutical product as a pharmacologically active compound (ingredient). (WHO GMP)

Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. (EU GMP Guide, Part 2)

APIs include substances manufactured by processes such as chemical synthesis; fermentation; recombinant DNA or other biotechnology methods; isolation/recovery from natural sources; or any combination of these processes. 

Acute Effects

Effects on the human body that occur a short time after exposure to a substance hazardous to death.

Active Sampling

A method of measuring the concentration of a gaseous contaminant in the atmosphere by drawing air through a filter medium onto which the contaminant will adsorb.

Advanced Technology Medicinal Product (ATMP)

Any one of the following: A gene therapy medicinal product; a somatic cell therapy medicinal product; a tissue-engineered product.

Adverse Drug Reaction (ADR)

All harmful an unintended responses to a medicinal product related to any dose.

Adverse Event (AE)

Any improper medical occurrence in a patient administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse effect (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Air Monitoring

The sampling for and measuring of contaminants in the air.

Airlock

An enclosed space with two or more doors, and which is interposed between two or more rooms, e.g. of differing class of cleanliness, for the purpose of controlling the air-flow between those rooms when they need to be entered. An airlock is designed for and used by either people or goods. (EU GMP Guide)

A small room with interlocked doors, constructed to maintain air pressure control between adjoining rooms (generally with different air cleanliness standards). The intent of an aseptic processing airlock is to preclude ingress of particulate matter and microorganism contamination from a lesser controlled area.

Airborne Particle Counter

Detects particulate contamination in controlled environments or anywhere particulate contamination is a concern.

Air-suit

A type of PPE comprising a complete suit with integral visor and breathable air supplied either from cylinders carried on the operator‘s back or by means of a flexible pipe linked to a remote source of clean air.

Alert Level

An established microbial or airborne particle level giving early warning of potential drift from normal operating conditions and triggers appropriate scrutiny and follow-up to address the potential problem. Alert levels are always lower than action levels.

Alert Limit

The alert limit is reached when the normal operating range of a critical parameter has been exceeded, indicating that corrective measures may need to be taken to prevent the action limit being reached. (WHO GMP)

Ambient Air

Any unconfined portion of the atmosphere: open air, surrounding air.

ANSI

American National Standards Institute

ASHRAE

American Society of Heating and Refrigeration Engineers

American Society for the Testing of Materials (ASTM)

Creates consensus standards for material quality and material quality testing methods

American Society of Mechanical Engineers (ASME)

Creates consensus standards for Mechanical Engineering

Anaerobic

Anaerobic pertains to the airless state. Refers to organisms that cannot live in the presence of air, in particular, oxygen.

Annual Product Review

FDA requirement: Evaluation (at least annually) of the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures. Written procedures shall be established and followed for such evaluations and shall include provisions for:

(1) A review of a representative number of batches, whether approved or rejected, and, where applicable, records associated with the batch.

(2) A review of complaints, recalls, returned or salvaged drug products, and investigations conducted under for each drug product.

(21 CFR 211.180 (e))

API Starting Material

A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API.

An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house.

API starting materials are normally of defined chemical properties and structure. (EU GMP Guide)

Asepsis

A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product.

Aseptic Process

A process using sterilized equipment before use, and which, in running conditions, is protected against re-contamination by micro-organisms. (EHEDG)

Operating in a manner that prevents contamination of the process.

Audit

An audit is a formal, independent, disciplined and objective review activity designed to assess the performance of an operation, a set of operations, a process or a system with regards to established regulations. In the field of GMP it is generally accepted to classify audits in internal audits (inside the same organization), second party audits (between two contractants) and third party audits (when using an independent auditor).

Autoclave

A piece of equipment used for steam sterilizing components “out of place”. In other works, parts must be placed into the autoclave for sterilization. “Autoclaving” also refers to the process of using an autoclave. NOTE: a component designed for SIP may not necessarily be autoclaved.

Auto-ignition

The lowest temperature at which a mixture of vapours, gases, and/or dusts in air will ignite spontaneously.

Auto-ignition temperature

The lowest temperature at which a mixture of vapours, gases and/or dusts in air will ignite spontaneously.

Automated Coupling Systems

Includes equipment that is capable of connecting through remote means and can include equipment that must dock and lock in place in order to operate.

Batch (Lot)

Means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture. (FDA Code of Fed. Regulations)

A defined quantity of starting material, packaging material or product processed in one process or series of processes that it could be expected to be homogeneous. (Note: to complete certain stages of manufacture, it may be necessary to divide a batch into a number of sub batches, which are later brought together to form a final homogeneous batch. In the case of continuous manufacture, the batch must correspond to a defined fraction of the production, characterized by its intended homogeneity.

For control of the finished product, the following definition has been given in Annex 1 of Directive 2001/83/EC as amended by Directive 2003/63/EC: ‘For the control of the finished product, a batch of a proprietary medicinal product comprises all the units of a pharmaceutical form which are made from the same initial mass of material and have undergone a single series of manufacturing operations or a single sterilization operation or, in the case of a continuous production process, all the units manufactured in a given period of time’. (EU GMP Guide, Glossary)

A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continuous production, a batch may correspond to a defined fraction of the production, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount produced in a fixed time interval. (EU GMP Guide, Part 2)

Batch Number

A distinctive combination of numbers and/or letters which specifically identifies a batch. (EU GMP Guide, Glossary)

A unique combination of numbers, letters, and/or symbols that identifies a batch (or lot) and from which the production and distribution history can be determined. (EU GMP Guide, Part 2)

Batch Record

All documents associated with the manufacture of a batch of bulk product or finished product. They provide a history of each batch of product and of all circumstances pertinent to the quality of the final product. (WHO GMP)

Documentation that provides the history of a batch from the raw material stage to the completion of a lot/batch.

Batch Splitting

Weighing out discrete quantities off-line of solids or liquids required for a process batch, either raw materials bought into the plant or intermediates made by previous process steps.

Bioburden

The total number of microorganisms associated with a specific item prior o sterilization. (FDA, Aseptic Guidance)

Biofilm

A microbial consortium adhering to a surface. (EHEDG)

Biogenerator

A contained system, such as a fermenter, into which biological agents are introduced along with other materials so as to affect their multiplication or their production of other substances by reaction with the other materials. Biogenerators are generally fitted with devices of regulation, control, connection, material addition and material withdrawal. (EU GMP Guide)

Biologic API

A material originating from a biological manufacturing process intended to furnish pharmacological activity or other direct effect in the cure, treatment, or prevention of disease or conditions of human beings. (FDA API Guide)

Biologic Product

Any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment, or cure of diseases or conditions of human beings. (FDA API Guide)

Biological Agents

Micro-organisms, including genetically engineered micro-organisms, cell cultures and endoparasites, whether pathogenic or not. (EU GMP Guide)

Biological Indicator (BI)

A population of microorganisms inoculated onto a suitable medium (e.g. solution, container or closure) and placed within appropriate sterilizer load locations to determine the sterilization cycle efficacy of a physical or chemical process. The challenge microorganism is selected based upon its resistance to the given process. Incoming lot D-Value and microbiological count define the quality of the BI.

Biosafety Cabinet

A special exhaust hood with an enclosed work surface for biological testing and experiments. Biosafety cabinets protect experiments from contaminants in the surrounding room, and they protect workers from hazardous materials being used in the cabinet. They also include features that prevent cross-contamination within the cabinet. Conventional fume hoods afford protection only for the room environment. Biosafety cabinet ventilation systems provide a flow of air from the room and through the fume hood face opening as well as HEPA filtering of exhaust and recirculating air. NSF 49

Biosafety Levels (BSL)

The rating of biohazard potential described in four degrees of severity: 1) BSL1 agents are low risk and not known to cause disease in healthy adult humans; 2) BSL2 agents are associated with agents known to cause human disease that can be moderately serious, and for which preventive or therapeutic interventions are often available; 3) BSL3 agents are indigenous or exotic with potential for infection following aerosol transmission, Agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available; 4) BSL4 organisms are dangerous/ exotic agents that pose a high risk of life-threatening disease, and for which preventive or therapeutic interventions are not usually available.

Blinding

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and doubleblinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). In relation to an investigational medicinal product, blinding shall mean the deliberate disguising of the identity of the product in accordance with the instructions of the sponsor. Unblinding shall mean the disclosure of the identity of the blinded products. (Annex 15 to EU GMP Guide)

Bracketting

An experimental design to test only the extremes of, for example, dosage strength. The design assumes that the extremes will be representative of all the samples between the extremes. (WHO GMP)

Breakthrough time

The time taken for a given chemical to pass through a given barrier.

Bulk Pharmaceuticals (BPs)

Mean materials (both pharmacologically active and inactive) which are intended for use as a component of a drug or biological product. These include materials manufactured by processes such as: (1) chemical synthetics; (2) fermentation; (3) recombinant DNA or other biotechnology methods; (4) isolation/recovery from natural resources, or (5) any combination of these processes. (US-API-Guide/Draft 1996)

Bulk Product

Any product that has completed all processing stages up to, but not including, final packaging. (EU GMP Guide)

Butterfly valve

A disc wherein the diameter of the pipe in which it is located and capable of rotating 90° about an axis through its diameter so that it either permits fluids or powders to flow past it or blocks the flow.

Calibration

The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established. (WHO GMP)

The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard. (EU GMP Guide, Glossary)

The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements. (EU GMP guide, Part 2)

CAPA (Corrective Action and Preventive Action)

System for implementing corrective actions and preventive actions resulting from the investigation of complaints, product rejections, non-conformances, recall, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring. (ICH Q10)

Capability

Ability of a process to realize of product that will fulfil the requirements of that product. The concept of process capability can also be defined in statistical term. (ICH Q10/ ISO 9000:2005)

Capture velocity

The minimum air velocity required to capture or divert by bulk air entrainment a cloud of dust or vapour into an exhaust hood.

Carcinogen

A substance liable to cause cancer if ingested, inhaled or otherwise taken in the body.

Category of danger

A description of hazard type as defined in CHIP, e.g. “harmful”, “irritant”, “sensitizer”, “toxic”.

Ceiling

1) The maximum allowable human exposure limit for an airborne substance no to be exceeded even momentarily. Used in OSHA PELs, ACGIH TLV, and NIOSH RELs. 2) The concentration that should not be exceeded during any part of the working exposure. In conventional occupational hygiene practice, if instantaneous monitoring is not feasible, the ceiling can be assessed by sampling over a 15-minute period, except for chemicals that may cause immediate irritation, even with exposures of extremely short duration.

Ceiling level

The maximum airborne concentration of a substance to which employees may be exposed at any time.

cGMP

Current perception of Good Manufacturing Practice as defined in US Federal Regulations and equivalent EU Directives.

CDER

Center for Drug Evaluation and Research. This is a division of the FDA that deals with the approval of new drugs and the inspection of pharmaceutical companies.

Cell Bank

Cell bank system: A cell bank system is a system whereby successive batches of a product are manufactured by culture in cells derived from the same master cell bank. A number of containers from the master cell bank are used to prepare a working cell bank. The cell bank system is validated for a passage level or number of population doublings beyond that achieved during routine production.

Master cell bank: A culture of (fully characterized) cells distributed into containers in a single operation, processed together in such a manner as to ensure uniformity and stored in such a manner as to ensure stability. A master cell bank is usually stored at – 70 ?C or lower.

Working cell bank: A culture of cells derived from the master cell bank and intended for use in the preparation of production cell cultures. The working cell bank is usually stored at – 70 ?C or lower. (EU GMP Guide)

Cell Culture

The result from the in-vitro growth of cells isolated from multicellular organisms. (EU GMP Guide)

Change Control

A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure and document that the system in maintained in a validate state. (Annex 15 to the EU GMP Guide)

Chemical

A common term for substances and preparations.

Chromatography

The purification of substances based upon chemical, physical, and biological properties of the molecules involved

Chronic effects

Effects on the human body that become apparent over a long period of time after exposure to a substance hazardous to health.

Clean Area

An area with defined environmental control of particulate and microbial contamination constructed and used in such a way as to reduce the introduction, generation, and retention of contaminants within the area. (EU GMP Guide)

Clean in Place

Automatic wet cleaning system of a line and/or equipment in a closed circuit without dismantling. Efficiency of CIP depends on the 5Ts: time, temperature, titration, turbulence and technology.

The technique of cleaning process line components without the need for disassembly.

The concept of automated cleaning of process-contact surfaces of equipment through spraying of cleaning solutions through spray balls and/or spray discs mounted inside the equipment. Clean-in-place systems are usually fed by skid mounted solution preparation and transfer stations or fixed stations in a manufacturing facility.

Clean Room

A room designed, maintained, and controlled to prevent particle and microbiological contamination of the products. Such a room is assigned and reproducibility meets an appropriate air cleanliness classification. (FDA Aseptic Guidance)

Cleaning Validation

Cleaning validation is documented evidence that an approved cleaning procedure will provide equipment which is suitable for processing medicinal products. (Annex 15 to the EU GMP Guide)

Clinical Trial

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and or other pharmacodynamics effects of an investigational product(s), and or to study absorption, distribution, metabolism, and excretion of one or more investigational medicinal product(s) with the object of ascertaining it/their safety and or efficacy. (Annex 13 to the EU GMP Guide)

Closed in-Line Sampling System

Systems that allow solution or powder contained sampling through a separate line directly connected to processing equipment. These systems prevent operator exposure during the sampling process by avoiding the use of “dip-legs” or spigots for solution sampling through the use of septum sampling stations and/or ventilated sampling stations. Typical vendors include Dopak, Neotecha and others.

Closed Systems

Equipment and containers that remain closed to the outer environment during operation or transfer (i.e. keeping the material inside the container or equipment to prevent release into the workroom, process area or ambient environment). This includes processing equipment capable of performing several steps (e.g. “one-pot” processors) and equipment that can be stacked “in-line” to allow gravity transfers. See also Direct Connections and Isolator/Glovebox Technology.

Closed Transfer

The movement of materials between two containers or between a container and process equipment through a closed system of pipes or ducts by direct connection.

Code of Federal Regulations (CFR)

The codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government. It is divided into 50 titles that represent broad areas subject to the Federal regulation.

Colony Forming Unit

A measure of bacterial contamination. Samples are incubated in a growth media (see PCA) and the resulting colonies are counted.

Commissioning

The setting up, adjustment and testing of equipment or a system to ensure that it meets all the requirements, as specified in the user requirement specification, and capacities as specified by the designer or developer. Commissioning is carried out before qualification and validation. (WHO GMP)

Comparator Product

An investigational or marketed product (i.e. active control), or placebo, used as a reference in a clinical trial. (Annex 13 to the EU GMP Guide)

Component

Any ingredient intended for use in the manufacturing of a drug product, including those that many not appear in such a drug product. (FDA Code of Fed. Regulations)

Compound Categorization

The grouping of active pharmaceutical ingredients (APIs) and chemical intermediates into occupational health categories based on their characteristics of potency and toxicity. Occupational health categories are usually linked to defined work environments and recommended handling practices to promote operator safety in general and to be used when no exposure limits (OEL, PEL, TLV) or air monitoring methods have been established. This approach is based on the same philosophu as the Biosafety Level system and was first applied to pharmaceuticals in a series of intra-industry workshops involving, Merck and Co., Eli Lilly, Abbott Laboratories, The Upjohn Company and Syntex (USA) Inc.

Computer System

A group of hardware components and associated software designed and assembled to perform a specific function or group of functions. (EU GMP Guide, Part 2)

Concurrent Validation

Validation carried out during routine production of products intended for sale (Annex 15 to the EU GMP Guide)

Containment

The action of confining a biological agent or other entity within a defined space.

Primary containment: A system of containment which prevents the escape of a biological agent into the immediate working environment. It involves the use of closed containers or safety biological cabinets along with secure operating procedures.

Secondary containment: A system of containment which prevents the escape of a biological agent into the external environment or into other working areas. It involves the use of rooms with specially designed air handling, the existence of airlocks and/or sterilizers for the exit of materials and secure operating procedures. In many cases it may add to the effectiveness of primary containment. (EU GMP Guide)

Containment Strategy

One of five generalized approaches proposed in this guide to limiting or eliminating exposures of personnel, products or the environment to hazardous concentrations of substance. Each provides protection at a specific level ranging from reliance on general ventilation for the removal of substances hazardous to health to total enclosure and mechanization of the process with all contact between the operator and substances hazardous to health eliminated.

Contamination

The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API during production, sampling, packaging or repackaging, storage or transport. (EU GMP Guide, Part 2)

Continuous Bag Systems (continuous drum liners)

Contained drum-loading systems which facilitate the safe transfer of bulk active pharmaceutical ingredients and intermediates, from process vessels into drums through the use of a continuous plastic liner and the crimp and cut technique for bag formation and separation.

Control Approach

One of four generalized approaches to exposure limiting/elimination, comprising reliance on general ventilation for the removal of substance hazardous to health, engineering control, containment and reliance on specialist expert advice.

Control Factor

A measure of the effectiveness of a control, being the ratio of the exposure obtained without the control to that obtained with the control operating.

Controlled Area

An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination (an air supply approximating to grade D may be appropriate) and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure negative to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. (EU GMP Guide)

Corrective Action

Action to eliminate the cause of a detected non-conformity or other undesirable situation. Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence. (ICH Q10/ ISO 9000:2005)

Critical

Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specifications. (EU GMP Guide, Part 2)

Critical Device

Any control, measuring, monitoring or testing device whose failure, including complete or partial failure, intermittent operation, ineffective operation or calibration defects, may have an adverse effect upon product quality, product security or the integrity of the complete process.

Critical Process Steps

Process steps that must be controlled within established operating ranges to ensure that the API or intermediate will meet specifications for quality and purity. (FDA API Guide)

Critical Stage

An operation during a production activity that, if not controlled within predetermined limits, may affect the product quality.

Critical Surfaces

Surfaces that may come into contact with or directly affect a sterilized product or its containers or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation, and sterility is maintained throughout processing.

Cross-Contamination

Contamination of a starting material, intermediate product, or finished product with another starting material or product during production. (WHO GMP)

Contamination of a material or of a product with another material or product (EU GMP Guide)

Cytotoxic

Harmful to cells.

Current Good Manufacturing Practices (cGMP)

Written and enforced by the FDA. Consists of some specific, but mostly “umbrella” regulations covering personnel, record, and equipment, leaving much to the interpretation of the inspector and the court system. cGMP are evolutionary, reflecting the least common denominator of practices in the industry at present (hence the term current)

Declaration of conformity

A quality control document that specifies the criteria to which a product was made and certifies that the product as supplied conforms to those criteria.

Decontamination

A process that eliminates viable bioburden via use of sporicidal chemical agents

Deionized or Deionization

The process of removing ionized salts from water by passing it through ion exchange (See IX and resin)

Deionized Water

Deionized water is deeply demineralized, ultrapure water with the resistivity close to 18 megohm-cm.

Deoxyribonucleic Acid

The chemical molecule that is the basic genetic material found in all cells. DNA is inherited. Because DNA is a very long, thin molecule, it is packaged into units called chromosomes. DNA belongs to a class of biological molecules called nucleic acids.

Depyrogenation

A process used to destroy or remove pyrogens (e.g. endotoxin)

Design Exposure Limit

Company-specific criteria established for the exposure-control performance of containment and control equipment. Generally 20% of OEL

Design Qualification (DQ)

The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose. (Annex 15 to the EU GMP Guide)

Design Space

The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (ICH Q8)

Dioctyl Phthalate

A mono-dispersed test aerosol of 0.3 micron particles, generated to challenge (evaluate integrity) of HEPA filters for HVAC.

Diffusive Sampling

A method of measuring the concentration of a gaseous contaminant in the atmosphere by allowing the contaminant to adsorb naturally onto a filter medium.

Dilution Ventilation

An alternative name for general ventilation.

Direct Connections

This concept relates to the transfer of material from one source to another and includes the ability to positively connect drums, charging systems, intermediate bulk containers, product bags and process equipment to other pieces of process equipment or receiving containers. This means there is no opening between the transfer containers/equipment and the receiving equipment.

Disinfection

The reduction, by means of chemical agents and/or physical methods of the number of micro-organisms in the environment to a level that does not compromise product safety or suitability. (EHEDG)

Dispensing

Another term for batch splitting.

Down flow booth

An enclosed area of a workplace into which air is supplied via the ceiling and from which it is extracted through a vent low down in the booth.

Distillation

The process of purifying water (or other liquid) by boiling the liquid and condensing the vapor. Most contaminants do not vaporize at the same temperature as the water and therefore, do not carry over to the distillate.

Distilled Water

The oldest method for production of pure water is the thermal method or distillation – water evaporation from the surface and condensation

DNA Typing

DNA typing is a technique for identifying individual organisms based upon the uniqueness of their DNA pattern. The technique has applications in forensics, paternity testing, anthropology, conservation biology and ecological research.

DQ

Design qualification, the preparation, as part of the validation process, of documented evidence that the design of equipment, facilities and operations complies with quality requirements.

Drug Product

Means a finished dosage form, for example, tablet, capsule, solution, etc. that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo. (FDA Code of Fed. Regulations)

DS

Design Specification, a complete definition of the equipment or system in sufficient detail and then built once the design has been approved.

Dry Heat Sterilization

Sterilization utilizing a heating oven or continuous tunnel (gas or electric heated), as opposed to steam sterilization in an autoclave, usually used for glassware and metal parts. In depyrogenation temperatures of 250 ?C result in sterilization and the inactivation of endotoxin present on the surface of ?

Dynamic Conditions

Environmental conditions of a manufacturing room occupied by the normal number of workers appropriately garbed and with production equipment in operation. However, dynamic conditions for some dusty operations, such as aseptic powder filling, may be measured in the absence of product.

Endotoxin

A component of the gram-negative organism’s cell wall. A pyrogen of specific concern in injectable solutions (see Gram-negative and Pyrogen). Endotoxins are not destroyed by temperatures that kill the bacteria themselves. They are measured by LAL. Endotoxin levels are specified for WFI (see WFI and LAL)

Engineering Control

The use of hardware, other than PPE, to control the physical environment in a manner that limits the exposure of individuals to the harmful effects of a particular hazard.

EP

Exposure potential, a measure of the risk arising from the use of a substance in a process, taking into account the toxicity and physical characteristics of the substance, the quantities used and duration of transfer of the substance into or out of the process.

Environmental Monitoring

The goal of an environmental monitoring program is to reveal the microbial levels of controlled and critical areas and to assess the impact on the quality of the product. By determining the quantity and species of organisms present, manufacturers can design a program to ensure the effectiveness of various control measures, such as HEPA filtration, disinfection, maintenance, gowning and aseptic processing technique.

Environmental Protection Agency (USA)

Agency that sets standards for potable water

Equipment Operating Procedure

(aka SOP, OP) A controlled document that outlines the procedure for operating equipment/system. An operator’s adherence to a written EOP is an integral part of the validation process. It is the connecting link between the initial validation process and the daily manufacturing operation.

European Pharmacopoeia

European counterpart to USP. A private non-profit? Organization that sets standards for drugs, drug ingredients, medical devices and diagnostics.

EU Directive

A legal document which has legal force across Europe, but which requires implementation in each Member State by means of local legislation

EU Guideline

Documents which provide guidance regarding certain topics (eg. GMP). A guideline is not intended to place any restraint upon the development of any new concepts or new technologies which have been validated and which provide a level of Quality Management at least equivalent to those set out in the Guideline. The GMP guide will be regularly revised in order to reflect continual improvement of best practices in the field of Quality.

EU Regulation

A legal document which has legal force and direct applicability across Europe.

EudraCT

A European database containing details of all clinical trials in Europe. Every clinical trial, which is subject to the Clinical Trials Directive, must be entered onto this database.

Expiration Date

The date (usually placed on the containers/labels of an API) designating the time during which the API is expected to remain within established shelf-life expectations if stored under defined conditions and after which it should not be used. (FDA API Guide)

The date placed on the container/labels of an API designating the time during which the API is expected to remain within established shelf life specifications if stored under defined conditions, and after which it should not be used. (EU GMP Guide)

Explosion Suppression

Introducing substances that will suppress an explosion as soon as it occurs.

Explosion Venting

The provision of pressure-relief panels on equipment or buildings that, in the event of an internal explosion, will blow out and so prevent the development of damaging excess pressures.

Exposure

1. As it pertains to air contaminants, it is the state of being exposed to a concentration of a contaminant. 2. Subjection of an employee in the course of employment to a chemical that is a physical or health hazard, and it includes potential (eg. Accidental or possible) exposure. “Subjected” in terms of health hazards includes any route of entry (eg. Inhalation, ingestion, skin contact or absorption) 3. Contact of an organism with a chemical or physical agent, quantified as the amount of chemical available at the exchange boundaries of the organism and available for absorption. 4. The amount of an environmental agent that has reached the individual (external dose) or has been absorbed into the individual (internal dose or absorbed dose)

Exposure Limit

A term use to cover OES, MELs and PELs

FDS

Functional Design Specification, a document detailing the functions to be carried out by a computer system and how they are achieved.

Flammable

Liable to burn or explode if ignited.

Flash point

The lowest temperature at which a liquid gives off sufficient vapour in sufficient concentration to form a combustible mixture with air near its surface.

Finished product

A product that has undergone all stages of production, including packaging in its final container and labelling. (WHO GMP)

A medicinal product which has undergone all stages of production, including packaging in its final container. (EU GMP Guide)

First Air

Air that passes over a critical component directly from a HEPA-filter that does not flow over equipment or personnel prior to flowing over the component.

Food and Drug Administration

Enforcement agency of the US Government for food, drug, and cosmetics manufacturing. Author of the US cGGMP. Responsible for new product approvals, plant inspections and product recalls.

Gas chromatography

A technique used during analysis of air samples to separate the various contaminants within a sample. An inert gas blows the sample through a column of adsorbent material. Molecule of different contaminants travel through the column at different rates and this enables their relative quantities in the sample to be measured.

General ventilation

Provision of an air supply or the reliance on natural air-flows to reduce the concentration of a contaminant released into the workplace.

Glove-box

An isolator filled with glove-ports.

Glove-port

A non-porous glove with long sleeves (generally elbow length) sealed into an opening in the wall of an isolator so as to maintain the containment provided by the isolator whilst allowing the operator to manipulate objects and controls inside it.

Good Manufacturing Practice

Refers specifically to FDA cGMP or to the standards of manufacturing in a particular country and industry (EU GMP). Generally refers to standards that are written and enforced.

Gram-Negative

One of two groups of bacteria, as determined by their ability to retain a dye after staining and rinsing. Those retaining the dye are Gram-positive. Those that do not retain the dye are Gram-negative. The differences are in the cell wall structure. The majority of water-borne bacteria are Gram-negative.

Gram-Positive

One of two groups of bacteria, as determined by their ability to retain a dye after staining and rinsing. Those retaining the dye are Gram-positive. Those that do not retain the dye are Gram-negative. The differences are in the cell wall structure.

HACCP

Systematic approach to the identification, evaluation and control of hazards at identified points within a production process in order to ensure the delivery of safe products to the patients. (internet see also Codex Alimentarius)

Hazard

The potential source of a harm. (ISO/IEC Guide 51)

Hazard group

In general, anything with the potential to cause harm to people or to the environment. In the context of this guide it normally means the potential harm that can arise from use of a substance, reflecting the inherently dangerous properties of that substance.

Into which a substance can be allocated depending on the severity of the hazard it presents to those exposed to it by inhalation.

HAZOP

Hazard and Operability study, a technique for performing a comprehensive analysis of a process to identify all the possible hazards it contains.

Health Hazard

A chemical for which there is statistically significant evidence based on at least one study conducted in accordance with established scientific principles that acute or chronic health effects may occur in exposed employees.

High Efficiency Particulate Air

Filters with a minimum efficiency of 99.97% for 0.3µm particle size as determined by test. The test can be done by the monodispersed dioctyl phthalate (DOP) method or other equally sensitive method. When operated at design velocity, larger and smaller particles are captured at higher efficiencies. HEPA filters are made of compressed and bonded microfiber glass or Teflon corrugated to produce a high surface area in a small area panel of filter medium. Employed in unidirectional airflow benches, air handlers, and as terminal air supply filters in cleanrooms.

Hierarchy of controls

A priority scheme for the selection of a control method for a hazard wherby elimination of the hazard is the preferred option, engineering controls and then administrative controls are applied if previous methods have failed to achieve adequate control and PPE is used only to control residual risk when all other methods have been applied and have reduced the risk to the greatest extent reasonably practicable.

Highly controlled area

An area to which no personnel have access and where complete emergency action plans and spillage procedures exist.

Hot Wire Anemometry

A technique for measuring air movement in an exhaust duct or at the face of a fumehood. Air is moved across a heated wire, cooling the wire. The measure of the wire’s change in resistance is directly related to the speed of the air. Also known as Thermal Anemometry.

Hood

The aperture through which an LEV system draws in contaminated air to be removed from a working area.

Horizontal laminar flow Hood booth

An enclosed area of a workplace from one closed end of which air is exhausted through a perforated distribution plate, which ensures that an even flow of air is drawn into the area from the open end.

HVAC

Heating, ventilating, and air conditioning system. Those systems that control and maintain the temperature, humidity, and air quality.

Impurity

Any component present in the intermediate or API that is not the desired entity. (EU GMP Guide, Part 2)

Impurity Profile

A description of the identified and unidentified impurities present in an API. (FDA API Guide and EU GMP Guide, Part 2)

Inactive Ingredient

Means any component other than an active ingredient. (FDA Code of Fed. Regulations)

Industrial Hygiene Sampling and Analytical Method

Detailed (and preferably validated for pharmaceuticals) laboratory procedures that specify how to collect and measure the amount of chemicals on sampling media. Methods are designed to characterize workplace exposures and are most valuable when they are sensitive enough to allow task-oriented monitoring.

Inerting

The replacement of air inside the process equipment with an inert gas (usually nitrogen) that will not affect the process but by excluding oxygen will prevent an explosive mixture from forming.

Inhalable Dust

Airborne material that is capable of entering the nose and mouth during breathing and is thereby available for deposition anywhere in the respiratory system.

In-Line Equipment

Process equipment that is located and fitted either directly or within a closed transfer line to allow gravity feeding and other types of material transfer without releasing the product or process intermediate to the workroom or ambient environment. See also Direct Connection.

In-Process Control

Checks performed during production on order to monitor and if necessary to adjust the process to ensure that the product conforms to its specifications. The control of the environment may also be regarded as a part of in-process control. (EU GMP Guide)

Checks performed during production in order to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or API conforms to its specifications. (EU GMP, Part 2)

In-Process Material

Means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product. (FDA Code of Fed. Regulations)

IQ

Installation Qualification, a documented demonstration, as part of the validation process, that facilities and equipment are installed as designed and specified.

Inspection

The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the manufacturing of a medicinal product, API or other starting material.

Installation Qualification

Documentation that an equipment/system has been installed properly according to the pre-determined codes and standards. This could include preventative maintenance procedures, spare parts lists, SOPs, part numbers, model numbers, serial numbers, capacities, performance data, material specifications, etc.

The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations. (Annex 15 to the EU GMP Guide)

Intermediate

A material produced during steps in the synthesis of an API that must undergo further molecular change or processing before it becomes an API. (FDA API Guide)

A material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (Note: this Guide only addresses those intermediates produced after the point that the company has defined as the point at which the production of the API begins)

Intermediate Bulk Containers (IBC)

Process containers that allow for direct connection to process equipment for gravity feeding into them and for inverting them (usually through the use of a lifting device) for subsequent gravity feeding to the next piece of equipment in the process. IBCs frequently are constructed with special dust-tight valves such as split butterfly valves. IBCs may also be used for transportation of products and process intermediates between facilities.

Intermediate Product

Partly processed material that must undergo further manufacturing steps before it becomes a bulk product. (EU GMP Guide)

In Situ

In place. In other words, without disassembly (see CIP and SIP)

In Vitro

Outside of the body

In Vivo

Inside of the body

International Standards Organization

Creates consensus standards for engineering and quality systems.

Intervention

An aseptic manipulation or activity that occurs at the critical zone.

Investigational Medicinal Product (IMP)

A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the authorized form, or when used for an unauthorized indication, or when used to gain further information about the authorized form. (Annex 13 to the EU GMP Guide)

Investigational Medicinal Product Dossier (IMPD)

Request for a clinical trial authorization (CTA) in the EU. An IMPD should include summaries of information related to the quality, manufacture and control of the IMP, data from non-clinical studies and from its clinical use. (Detailed guidance for the request for authorization of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial).

Investigational New Drug (IND)

FDA Application for a clinical trial investigation: the sponsor shall submit an IND to FDA if the sponsor intends to conduct a clinical investigation with an investigational new drug. (FDA Code of Federal Regulations, 21 CFR 312)

Investigator

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. (Annex 13 to the EU GMP Guide)

Ion Exchange

A process in which specific ions are removed from a solution in exchange for equivalently charged ions. The exchange process takes place on the surface of small particles called resins.

Isolator/Glovebox Technology

An industry-specific controlled environment enclosure providing a primary barrier from the work area. The operation is performed through sealed glove openings to protect the worker, the ambient environment and/or the product. Isolators usually feature ergonomic design features, contained means of moving material in and out and the ability to control ambient conditions inside the unit.

Isopropyl Alcohol

Commonly used sanitizing agent

Key Intermediate

Means an intermediate in which at least one essential molecular characteristic, usually involving the proper stereochemical configuration required for structure or pharmacological/physiological activity, is first introduced into the molecular structure. (US-API-Guide/Draft 1996)

Knowledge Management

Systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components. (ICH Q9, ICH Q10)

Laminar Airlow

An airflow moving in a single direction and in parallel layers at constant velocity from the beginning to end of a straight line vector.

Large Volume Parenteral

Injectable solutions for humans. Greater than 100ml for a single dose.

Sterile solutions intended for parenteral application with a volume of 100ml or more in one container of the finished dosage form. (WHO GMP)

Limit of detection (analytical chemistry)

The lowest amount of analyte in a sample which can be detected but not quantitated as an exact value. The Limit of Detection is mostly a parameter of limit tests. (PIC/S)

Limit of detection (Microbio)

In the context of the validation of a qualitative microbiological method the limit of detection is the lowest number of mico-organisms in a sample that can be detected. A microbiological limit test determines the presence or absence of micro-organisms. Due to the nature of microbiology, the limit of detection refers to the number of micro-organisms present in the original sample before any dilution or incubation steps; it does not refer to the number of micro-organisms present at the time of testing.

Limit of quantification (analytical chemistry)

The lowest amount of analyte in a sample whih can be quantitatively determined with defined precision and accuracy under the stated experimental conditions. (PIC/S)

Limit of quantification (Microbio)

In the context of the validation of a quantitative microbiological method the limit of quantification is the lowest number of micro-organisms that can be accurately counted.

Limiting oxygen Concentration

The percentage of oxygen in an atmosphere above which the atmosphere becomes explosive.

Limited venting

Exhausting excess gases into a confined area in the event of an explosion.

Limulus Amebocyte Lysate

A material obtained by rupturing the cellular components of the blood of a horse shoe crab (Limulus Poliphemus). This material coagulates in the presence of LPS (lypopolysaccharides) and is a test used to quantitate bacterial endotoxins (pyrogens)

Liquid Chromatoraphy

A technique similar to gas chromatography, in which a liquid solvent is used in place of the inert gas to transport the sample through the adsorbent column.

Long term exposure

The airborne concentration of a chemical in a person‘s breathing zone, calculated as a TWA over 8 hours.

Lot

Means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits. (FDA Code of Fed. Regulations)

Lot Number

Control number, or batch number means any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. (FDA Code of Fed. Regulations)

Low Dust Generating Operation

Pharmaceutical or chemical operation that generates little airborne material during normal functioning. Judgment is required in this determination; however in general, this includes operations where the airborne dust level is just visible to levels where it is invisible. Pure API-handling operations are usually excluded from this definition as well as known high dust generating operations such as milling, micronizing, sieving and sieve shaking, manual scooping and dumping overhead etc.

Lyophilization

Also known as freeze drying, it is a means of stabilizing wet substances by freezing them, then evaporating the resulting ice, to leave a substantially dry, porous residue which has the same size and shape of the original frozen mass.

Lyophilizer

A freeze dryer

LEL

Lower Explosive Limit, the concentration of gas or vapour in air below which the gas atmosphere cannot be ignited.

LEV

Local Exhaust Ventilation, a system for drawing air in the immediate vicinity of a source of contamination away from those working in the area.

LFL

Lower Flammable Limit, the concentration of gas or vapour in air below which the gas atmosphere is not flammable. In practice, identical to LEL

Machine

A piece of equipment that has moving parts and, usually, some kind of drive unit.

Manufacture

All operations of purchase of materials and products, production, quality control, release, storage, shipment of finished product, and the related controls. (EU GMP Guide, Glossary)

All operations of receipt of materials, production, packaging, repackaging, labelling, relabeling, quality control, release, storage, and distribution of APIs and related controls. (EU GMP Guide, Part 2)

Manufacturer

A company that carries out at least one step of manufacture. (WHO GMP)

Holder of a Manufacturing Authorization as describe in Article 40 of Directive 2001/83/EC (EU GMP Guide)

Manufacturing Authorization

Competent Authority permission to manufacture a medicinal product.

Marketing Authorization (product license, registration certificate)

A legal document issued by the competent drug regulatory authority that established the detailed composition and formulation of the product and the pharmacopoeial or other recognized specifications of its ingredients and of the final product itself, and includes details of packaging, labelling, and shelf-life. (WHO GMP)

Master Formula

A document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the in-process controls. (WHO GMP)

Master Record

A document or set of documents that serve as a basis for the batch documentation (blank batch record) (WHO GMP)

Mated

See Direct Connection

Materials

A general term used to denote Raw Materials, Process Aids, Intermediates, Active Ingredients and Packing Materials. (EU GMP Guide)

Medicinal Product

Any substance or combination of substances presented for treating or preventing disease in human beings or animals.

Any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting, or modifying physiological functions in human beings or in animals is likewise considered a medicinal product. (EU GMP Guide)

MEL

Maximum Exposure Limit, the maximum permissible concentration of a chemical to which personnel may be exposed measures as a TWA over a stated reference period (15 minutes for short-term limits; 8 hours for long-term limits); set for substances that may cause serious health effects and for which either no safe levels exist or control to safe levels is not reasonably practicable. Exposures to such substances should be reduced so far as is reasonably practicable but must never be allowed to attain or exceed the MEL.

Methods Validation

Means the documented successful evaluation of an analytical methods that provides a high level of assurance that the method will consistently yield reliable and accurate results, within previously established specifications. (US-API Guide/Draft 1996)

Microbiological Air Sampler

An air sampler that works by drawing calibrated volumes of air through an instrument that contains a petri dish with culture media specifically designed to grow either fungi or bacteria.

Microbiology

The study of organisms that are too small to be seen with the naked eye, such as bacteria, viruses and yeasts

Monitoring

The act of conducting a planned sequence of observations or measurements of control parameters to assess whether a defined process is under control. (EHEDG)

MSDS

Material Safety Data Sheet, information that must be provided as part of the supply requirements.

Multiple Effect (Distillation)

An energy efficient distillation process (see distillation) where the steam generated in one stage is used to heat the liquid in the next stage, up to 10 or more stages or “effects”

Mutagen

A substance liable to change genes if ingested, inhaled or otherwise taken into the body.

National Institutes of Health

The US Government’s central laboratories for biomedical research (both self-performed and sponsored). Comprised of 27 separate components, mainly Institutes and Centers, the NIH has 75 buildings on more than 300 acres in Bethesda, MD. The NIH budget stood as more than $20.3 billion in 2001. Of special importance in biomedical research funding because of the amount of funding provided, the prestige attached to its grants and the rigorous peer-review process under which grants are awarded.

Near-missed event

An incident that, if not detected in a timely manner, would have affected the safety of the recipients or donors. (WHO GMP for Blood Products)

New Chemical Entity (NCE)

Means a chemical that has not been adequately characterized in the literature regarding its physical and chemical properties. (USP-API-Guide/Draft 1996)

New Drug Application

A document submitted to the FDA to obtain a license for a new drug.

New Molecular Entity (NME)

The designated therapeutic moiety (API) in a dosage form that has not been approved for marketing in the US (also referred to as a new chemical entity or new drug substance). It may be a complex, simple ester or salt of a previously approved API. (FDA API Guide March 1998)

NIOSH

National Institute of Occupational Safety and Health

Non conformance

Failure of a process, procedure or application thereof or resulting product to comply with one or more specific quality criteria.

Non-conforming material

Any material that does not meet manufacturer’s specifications or applicable GMPs

Non-unidirectional airflow

Air distribution where the first air entering the controlled space mixes with the internal air by means of induction. The airflow that does not meet the definition of unidirectional airflow; previously referred to as “turbulent” or “non-laminar” airflow

Occupational Exposure Limit (OEL)

Industry or other non-governmental exposure limit (frequently established by pharmaceutical companies for their products) and usually based on scientifically defensible calculations of levels of material in air considered to be acceptable for healthy workers. Limits are usually expressed as 8-hour time weighted averages for exposures for 40 hours a week over a working lifetime (see Permissible Exposure Limit). OELs may also be protective for sensitive subpopulations of the healthy workforce (eg. Women of childbearing potential, asthmatics)

Operational Qualification

Demonstration and documentation of the equipment/system/s functionality. Used to prove the operational limits of the equipment/system, often run on a product substitute to prove functionality prior to running on product-for-sale. Other items tested could include failure mode, alarm features and cleanability. Typically executed by the commissioning team.

The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges. (Annex 15 to the EU GMP Guide)

Operator

Any individual participating in the aseptic processing operation, including line set-up, filler, maintenance, or other personnel associated with aseptic line activities.

Open Transfer

The movement of materials between containers by scooping or pouring from one container to another.

OOS (Out of Specification)

The term OOS Results includes all test results that fall outside the specifications or acceptance criteria established in product files or by the manufacturer. (FDA OOS Guidance)

OOS (Out of Limit, Microbio)

A result of microbiological monitoring exceeded the defined (by guideline or internal) limit of detection, eg. On surfaces – it is a deviation which requires normally an investigation and CAPA procedure

OQ

Operational Qualification, a documented demonstration, as part of the validation process, that facilities and operations function as specified throughout the anticipated operating stages.

OSHA

Occupational Safety and Health Administration

Over Exposure

Repeated measurements over established limits (PEL, TLV, OEL) and or documented incidents of occupational illness or disease.

Outsourced Activities

Activities conducted by a contract acceptor under a written agreement with a contract giver. (ICH Q10)

Ozonation

The use of ozone (O3) to disinfect water. Ozone is added to water and then neutralized using ultraviolet (UV) light.

Packaging

All operations, including filling and labelling, that a bulk product has to undergo in order to become a finished product. Sterile filling would not be normally be regarded as part of packaging, the bulk product being the filled, but not the finally packaged, primary container. (WHO GMP)

All operations, including filling and labelling, which a bulk product has to undergo in order to become a finished product. Note Sterile filling would not normally be regarded as a part of packaging, the bulk product being the filled, but not finally packaged, primary containers. (EU GMP Guide)

Packaging Material

All material, including printed material, employed in the packaging of a pharmaceutical product, excluding any outer packaging used for transportation or shipment. Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product (WHO GMP)

Any material employed in the packaging od a medicinal product, excluding any outer packaging used for transportation or shipment. Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product. (EU GMP Guide, Glossary)

Any material intended to protect an intermediate or API during storage and transport. (EU GMP Guide, Part 2)

Parenteral Drug

A parenteral drug is defined as one intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal, so that active substances the contained are administered, using gravity or force, directly into a blood vessel, organ, tissue, or lesion. They are infused when administered intravenously (IV) or injected when administered intramuscularly (IM), or subcutaneously into the human body. A large volume parenteral (LVP) is a unit dose container of greater than 100ml that is terminally sterilized by heat. Small volume parenteral (SVP) is a “catch-all” for all non-LVP parenteral products except biologicals.

Parenteral Drug Association

Association for manufacturers of injectable drug products. Publishes technical reports and other publications of interest to the industry.

Particle

Solid or liquid object which for purposes of classification of air cleanliness, falls within a cumulative distribution that is based upon a threshold (lower limit) size in the range from 0.1 µm to 5 µm. ISO 14644-1

Penetration

The gradual transfer of material through holes in an apparently solid barrier.

Permeation

The gradual transfer of molecules of a liquid or gas by diffusion between the molecules of a solid barrier.

Permeation rate

The rate at which a chemical passes through a given sample of a material.

Percentage of Theoretical Yield

Means the ratio of the actual yield (at any appropriate phase of the manufacture), processing or packaging of a particular drug product) to the theoretical yield (at the same phase), stated as percentage. (FDA Code of Fed. Regulations)

Performance-Based Exposure Control Limits (PB-OCLs)

Exposure control categories that dictate the level of control necessary for given operations to maintain risks at acceptable levels (ie, the level of containment or exposure control is commensurate with the risk)

Performance Qualification (PQ)

The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification. (Annex 15 to the EU GMP Guide)

Permissible Exposure Limit (PEL)

Established by OSHA (see 29 CFR 1910.1000, Subpart Z). The permissible concentration in air of a substance to which nearly all workers may be repeatedly exposed 8 hours a day, 40 hours a week, for 30 years without adverse effects

Personal Protective Equipment

Equipment (eg. Gloves, eye protection, respirators) designed to protect individuals from hazards or biohazards

PQ

Performance Qualification, a programme of documented testing, as part of the validation process, to show that a system (or group of systems), when performing with process material within product-specific design parameters, will consistently meet predetermined acceptance criteria.

Pest

Includes birds, bats, rodents and insects whose uncontrolled presence affects hygiene and cleanliness. (WHO GMP)

Pharmaceutical Product

Any medicine intended for human use or veterinary product administered to food-producing animals, presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in both the exporting state and the importing state. (WHO GMP)

A chemical for which there is scientifically valid evidence that it is a combustible liquid, a compressed gas, explosive, flammable, an organic peroxide, an oxidizer, pyrophoric, non stable (reactive) or water-reactive.

Pivotal Intermediate

Means an intermediate that may be prepared by more than one manufacturing process to provide material of suitable quality for use in the production of an API. (US-API-Guide/Draft 1996)

Placebo

A harmless chemical substituted for a substance hazardous to health during OQ to enable the performance of a process to be simulated without the danger of exposing people to that harmful substance in the event of a leak, rupture or other incident.

Plate Count Agar

The most common growth media for measuring bacteria levels (see CFU)

Potent Compound

1) A pharmacologically active ingredient or intermediate with biological activity approximately 150 micrograms per kilogram of body weight or below in humans (therapeutic dose at or below 10 mg). 2) An active pharmaceutical ingredient or intermediate with an OEL at or below 10 micrograms per cubic meter of air as an 8-hour time weighted average. 3)A pharmacologically active ingredient or intermediate with high selectivity (ie, ability to bind to specific receptors or inhibit specific enzymes) and/or with the potential to cause cancer, mutations, developmental effects or reproductive toxicity at low doses. 4) A novel compound of unknown potency and toxicity

Powered Air-Purifying Respirator

An air-purifying respirator that uses a blower to force the ambient atmosphere through air-purifying elements to the inlet covering.

Precision (quantitative method)

In the context of the validation of a quantitative Rapid Microbiological Method the precision is the degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of homogeneous suspensions of micro-organisms The precision is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements.

Preferred Analytical Sensitivity

The ability to detect 10% of the OEL of a given compound in a 15-minute air monitoring sample. Acceptable analytical sensitivity may be the ability to detect 20% of the OEL of a given compound in a 1-hour air monitoring sample

Preparation

A mixture of substances.

Pressure Cascade

A process whereby air flows from one area, which is maintained at a higher pressure, to another area at a lower pressure (WHO GMP)

Preventive Action

Action to eliminate the cause of potential non-conformity or other undesirable potential situation. Prevention action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. (ICH Q10, ISO 9000:2005)

Pressure -Shock Resistance

The ability of an item of equipment or a part of a building to retain its structural integrity under the impact of a rapid pressure rise caused by a dust or vapour explosion.

Production control System

Computer systems, including all of the associated hardware and software, whose purpose is to control production equipment and/or process parameters.

Primary and Secondary Dust Collection

Dust collection systems for particle removal from exhaust systems may include several types of filtration mechanisms. A collector for fine particle removal may only contain a single filtration system (such as a filter bag or cartridge). However, some units utilize a primary and secondary separation / filtration system and such systems are recommended. Furthermore, collection units may be designed and equipped with third and fourth stage filtration. Systems with contained filter changing (eg. Bag in bag out) are preferred and recommended for potent compound handling areas.

Procedures

Description of the operations to be carried out, the precautions to be taken and measures to be applied directly or indirectly related to the manufacture of a medicinal product. (EU GMP)

Process Aids

Materials, excluding solvents, used as an aid in the manufacture of an intermediate or API that do not themselves participate in a chemical or biological reaction (eg filter aid, activated carbon, etc) (EU GMP Guide)

Process Qualification/Process Validation

The demonstration and documentation that the various units and procedures of a process operate as they should. This logically establishes that the product is of the quality the system as purported to yield. Performed after the IQ/OQ has been executed and approved. Typically the acceptance criteria are the same, as the product run is considered product-for sale. Executed by the manufacturing personnel of the operating company according to the SOP.

Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. (FDA API Guide)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. (Annex 15 to the EU GMP Guide)

Product Quality Review (PQR)

Part of Chapter 1 “Quality Management” of the EU-GMP Guide is the Product Quality Review (PQR).  The aim of this requirement – that has to be fulfilled for all licensed medicinal products – is to verify

1. The consistency an appropriateness of the existing process

2. The adequacy of current specifications for starting material and finished product

3. and to identify product and process improvements

The PQR covers all aspects of the supply chain: Starting materials, process, process environment and product.

Product Specification File (PSF)

A reference file containing, or referring to files containing, all the information necessary to draft the detailed written instructions on processing, packaging, quality control testing, batch release and shipping of an investigational medicinal product.

The purpose of this file is described its role as the basis for assessment of the suitability for release and certification of a particular batch. The information contained in the PSF must be taken into account in the drawing up of all important work instructions. (Annex 13 to the EU GMP Guide)

Production

All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing and packaging, to completion of the finished product. (EU GMP Guide)

Programmable Logic Controller

An automated system with analog capability as well as binary (discrete). PLCs must be equipped with a digital interface to a “front end” computer for data collection and for programmer interface

Prospective Validation

Establishing documented evidence that a system does what it purports to do prior to the commercial distribution of a new API or an existing API made by a new or modified process (FDA API Guide)

Validation carried out before routine production of products intended for sale. (Annex 15 to the EU GMP Guide)

Purification Procedure

A process, such as crystallization, distillation, or chromatography, intended to improve the purity of an API or intermediate. (FDA API Guide)

Pyrogen

Any substance capable of producing a fever in humans. Most commonly organic substances shed by bacteria. Pyrogens are not necessarily destroyed by conditions that kill bacteris. (see Endotoxin)

Qualification

Action of proving that any equipment works correctly and actually leads to the expected results. The word validation is sometimes widened to incorporate the concept of qualification. (EU GMP Guide, Glossary)

Action of proving and documenting that equipment or ancillary systems are properly installed, work correctly, and actually lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation. (EU GMP Guide, Part 2)

Qualified Person

The person defined in Article 48 of Directive 2001/83/EC and Article 52 of Directive 2001/82/EC. Each batch of finished product must be certified by a QP within the EC/EEA before being released for sale or supply in the EC/EEA or for export.

Quality

The degree to which a set of inherent properties of a product, system or process fulfills requirements. See ICH Q6A definition specifically for “quality” of pharmaceutical substances and products. (ICH Q9)

Quality Assurance

The sum total of the organized arrangements made with the object of ensuring that all APIs are of the quality required for their intended use and that quality systems are maintained. (EU GMP Guide, Part 2)

Quality Control

Checking or testing that specifications are met. (EU GMP Guide, Part 2)

Checking or testing that specifications are met, or the regulatory process through which the industry measures actual quality performance, compares it with standards, and acts on the difference,

Quality Control Unit

Means any person or organizational element designated by the firm to be responsible for the duties relating to quality control. (FDA Code of Fed. Regulations)

Quality Manual

Document specifying the quality management system of an organization. (ICH Q10, ISO9000:2005)

QRM (Quality Risk Management)

A systematic approach for the assessment, control, communication and review of risks to the quality of the product across the product lifecycle. (ICH Q9)

Quality Unit

An organizational unit independent of production which fulfils both quality Assurance and Quality Control responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization. (EU GMP Guide, Part 2)

Quarantine

The status of starting or packaging materials, intermediate, bulk or finished products isolated physically or by other effective means whilst awaiting a decision on their release or refusal. (EU GMP Guide, Glossary)

The status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection. (EU GMP Guide, Part 2)

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. (Annex 13 to the EU GMP Guide)

Range (analytical chemistry)

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.

Range (Microbio)

In the context of the validation of a quantitative microbiological method the range is the interval between the upper and lower levels of microorganisms that have been determined with precision, accuracy, and linearity using the method as written. The range is determined from studies of precision, accuracy and linearity.

Rapid Transfer Ports

Specially designed devices usually found on isolation systems that allow quick connection and disconnection through docking and locking and proved the isolation system with a means to transfer material in and out of the units in a contained manner. These may include alpha/beta devices (also known as DPTEs), alpha/beta bags and similar technology.

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 2)

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)

Recovery

The introduction of all or part of previous batches of the required quality into another batch at a defined stage of manufacture. (EU GMP Guide)

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 recognized 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 2)

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 2)

Relaxation Time

The time required for powder settling inside of process equipment. This term is frequently used to describe the time necessary for power to settle inside of a fluid bed dryer prior to opening.

Remote-Slit Sampler

Air Sampler that pulls air through a slit barrel onto a rotating 150 mm agar plate for incubation and colony counting.

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 (eg distillation, filtration, chromatography, milling) that re 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 2)

Retest Date

The date when a material should be re-examined to ensure that it is still suitable for use. (EU GMP Guide, Part 2)

Retrospective Validation

Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data. (Annex 15 to the EU GMP Guide)

Return

Sending back to the manufacturer or distributor of a medicinal product which may or may not present a quality defect. (EU GMP Guide)

Returned Product

Finished product sent back to the manufacturer. (WHO GMP)

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. (Annex 15 to the EU GMP Guide)

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 (eg recrystallizing with a different solvent). (EU GMP Guide part 2)

Risk

A measure of both the severity of a hazard and the likelihood that it will result in actual harm to people or to the environment.

Robustness (analytical chemistry)

Measure of an analytical procedure’s capacity to remain unaffected by small, but deliberate, variations in method parameters and provides an indication of its reliability during normal usage.

Robustness (Microbio)

In the context of the validation of a microbiological method the robustness is a measure of its capacity to remain unaffected by small but deliberate variations in method parameters, and provides an indication of the method’s reliability under a variety of normal test conditions, such as different analysts, instruments, batches of reagents and laboratories. Robustness can be defined as the intrinsic resistance to the influences exerted by operational and environmental variables on the results of the microbiological method.

RPE

Respiratory Protective Equipment, PPE specifically designed to protect the wearer from inhaling dangerous concentration of chemicals. It ranges from simple filters over the mouth and nose to self-contained breathing apparatus.

RTP

Rapid Transfer Port, a port assembly used to provide contained transfer directly between an isolator and a container. The port doors on such assembly can open only if it is docked with another matching assembly.

Sampling train

A combination of sampling head, including a suitable filter medium, and a pump that draws air through the filter; used to measure airborne contamination.

Self-Inspection

An internal evaluation of the manufacturer’s compliance with GMP in relevant aspects of production and quality control. (WHO GMP)

Skin Notation

Denotes the possibility that dermal absorption may be a significant contribution to the overall body burden of the chemical (that is, the airborne OEL might not be adequate to protect the worker because the compound also readily penetrates the skin. Other toxicity endpoints on skin such as irritation, dermatitis, and sensitization are not sufficient to warrant the skin notation. In practice, the skin notation is given to compounds with a dermal LD50 less than 1000mg/kg, or if there are other data indicating that repeated dermal exposure results in systemic toxicity.

Short-Term Exposure Limit (STEL)

1) Maximum concentration for continuous 15-minute period. Allowed four times a day, with at least 60 minutes between exposures. 2) Used in reference to the OSHA PEL-STEL and ACGIH’s TLV-STEL. The STEL represents a time-weighted average (TWA) exposure that should not be exceeded for any 15-minute period. 3) STELs are recommended when exposures of even short duration to high concentrations of a chemical are known to produce acute toxicity. It is the concentration to which workers can be exposed continuously for a short period of time without suffering from 1. Irritation, 2. Chronic or irreversible tissue damage or 3. Narcosis of sufficient degree to increase the likelihood of accidental injury, impaired self-rescue, or reduced work efficiency. A STEL is defined as a 15-minute TWA exposure that should not be exceeded at any time during a workday, even if the overall 8-hour TWA is within limits, and it should not occur more than four times a day. There should be at least 60 minutes between successive exposures in this range. If warranted, an averaging period other than 15 minutes can also be used. 4. Generally three times the OEL for pharmaceuticals.

SMACNA

Sheet Metal and Air Conditioning Contractors’ National Association

Specification

A document describing in detail the requirements with which the products or material used or obtained during manufacture have to conform. Specifications serve as a basis for qualify evaluation. (WHO GMP)

A list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a drug substance or drug product should conform to be considered acceptable for its intended use. “Conformance to Specifications” means that the drug substance and / or drug product, when tested according to the listed analytical procedures, will meet the listed acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities. (ICH Q6A October 1999)

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 2)

Specificity

In the context of the validation of a Rapid Microbiological Method the specificity is its ability to detect the required range of microorganisms that may be present in the sample under test. For those methods that do not require growth as an indicator of microbial presence, the specificity assures that extraneous matter in the test system does not interfere with the test. Where relevant for the purpose of the test, mixtures of micro-organisms are used during validation.

Split Butterfly Valve (SBV)

Equipment and container docking system made up of an active and a passive split valve, which, independently from one another, seal the two container/receivers in a relatively dust-free connection. Product transfer is made possible by bringing together both split valves and opening them. This technology does not allow the product to come into contact with the working environment. The docking, undocking and transfer processes significantly reduces material airborne release compared to simple butterfly valves, open transfers and other traditional systems.

Sponsor

An individual, company, institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial. (Annex 13 to the EU GMP Guide)

Standard Operating Procedure

An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (eg. 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

Step-over

The dividing feature (typically a bench in a changing room adjoining a room where hazardous materials are processed) at which an operator changes from external clothing in clean or other protective work clothes. Having made the change, the operator must not cross the feature again but must leave the hazardous area via a suitable decontamination area.

Starting Material

Any substance used in the production of a medicinal product, but excluding packaging materials. (EU GMP Guide)

Sterility

Sterility is the absence of living organisms. The conditions of the sterility test are given in the European Pharmacopoeia. (EU GMP Guide)

Strength

Means that 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). (FDA Code of Fed. Regulations)

Substance

A chemical element or one of its compounds, including any impurities.

Substance hazardous to health

A substance that can harm human health if it is inhaled or ingested or if it comes into contact with the skin.

Suitable and sufficient assessment

An assessment of the risks to health arising from substances hazardous to health, the practicability of the prevention of exposure to those substances, the identification of the steps that need to be taken to achieve adequate control of exposure where prevention is not reasonably practicable and any other action needed to prevent harm arising from the presence of such substances.

System

Is used in the sense of a regulated pattern of interacting activities and techniques which are united to form an organized whole. (EU GMP Guide)

Technical area

The area of a facility in which production support and ancillary equipment are located or in which products are never exposed, which can be designed to lower environmental standards than process area.

Theoretical Yield

Means the quantity that would be produced at any appropriate phase of manufacture, processing, or packaging or a particular drug product, based ipon the quantity of components to be used, in the absence of any loss or error in actual production. (FDA Code of Fed. Regulations)

The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production. (EU GMP Guide, Part 2)

Threshold Limit Value (TLV)

Used by the ACGIH to designate degree of exposure to contaminants and expressed as parts of vapor or gas per million parts of air by volume at 25 ?C and 760 mmHg pressure, or as an approximate milligrams or particulate per cubic meter of air (mg/m3). An exposure level under which most people can work consistently for 8 hours a day, day after day, with no harmful effects. TLV are listed as either an 8-hour TWA or a 15-minute STEL.

Time Weighted Average

1) Average exposure for an individual over a given working period, as determined by sampling at given times during the period. 2) The most frequently used exposure guideline term; the average concentration over a work day (8 hours for OSHA PELs and ACGIH TLV, up to 10 hours in a 40 hour workweek for NIOSH Recommended Exposure Limits). 3) This is the fundamental concept of most occupational exposure limits (OEL) It is usually presented as the average concentration over a 8-hour workday for 40 hour workweek; however, this implies that concentrations will be both above and below the average value. The ACGIH TLV committee has recommended excursion limits to prevent concentrations form severely exceeding the average value. The proposed excursion limits are that exposures should typically not exceed the TWA by more than threefold and for a period not exceeding 30 minutes during the workday. Even if the TWA is not exceeded for the work shift, in no case should the excursion be more than fivefold the TWA value.  

Toxic

(Of a substance) able to damage human tissue or organs so as to cause illness or death.

TWA

Time-Weighted Average, an average value of a parameter calculated by summing multiples of all values of the parameter by the total duration.

Trend

A statistical term referring to the direction or rate of change of a variable(s). (ICH Q9)

Unidirectional flow

An airflow moving in a single direction, in a robust and uniform manner, and at a sufficient speed to reproducibly sweep particles away from the critical processing or testing area.

United States Pharmacopoeia

A private, non-profit organization that sets standards for drugs, drug ingredients, medical devices and diagnostics. The Food, Drug, and Cosmetic Act recognizes the USP and the National Formulary (both written by the USPC) and obligates the FDA to enforce its established standards. The USP contains the standards for WFI and Purified Water.

Validation

Action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity, or system actually leads to the expected results (see also qualification). (EU GMP Guide, Glossary)

A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria. (EU GMP Guide, Part 2)

Validation Protocol

A written plan stating how validation will be conducted and identifying specific acceptance criteria. For example, the protocol for a typical manufacturing process identifies processing equipment, critical process parameters/operating ranges, product characteristics, sampling and test data to be collected, number of validation runs, and acceptable test results. (FDA API Guide)

A written plan stating how validation will be conducted and defining acceptance criteria. For example, the protocol for a manufacturing process identifies processing equipment, critical process parameters/operating ranges, product characteristics, sampling, test data to be collected, number of validation runs, and acceptable test results. (EU GMP Guide, part 2)

Validation Master Plan

Validation master plan is a high-level document which establishes an umbrella validation plan for the entire project, and is used as guidance by the project team for resource and technical planning (also referred to as master qualification plan). (WHO GMP)

Water for Injection

WFI is water purified by distillation or by reverse osmosis, it contains no added substance. WFI meets the purity requirements under purified water. Although not intended to be sterile, it meets a test for a limit of bacterial endotoxin. It must be produced, stored, and distributed under sterile water for injection.

Working Standard

An API, intermediate or other substance of established quality and purity, as shown by comparison to a primary reference standard, used as a reference for routine laboratory analysis. (FDA API Guide)

Worst Case

A condition or set of conditions encompassing upper and lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure (Annex 15 to the EU GMP Guide)

Yield, Actual

Means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packaging of a particular drug product. (FDA Code of Fed. Regulations)

Yield, Expected

The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale, or manufacturing data. (EU GMP Guide, Part 2)

Yield, Theoretical

The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production. (EU GMP Guide, Part 2)