GMP Definitions

A.

Accelerated testing: Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. Data from these studies, in addition to long-term stability studies, can be used to assess longer term chemical effects at non-accelerated conditions, and to evaluate the effect of short-term excursions outside the label storage conditions, such as might occur during shipping. Results from accelerated testing studies are not always predictive of physical changes.

Acceptance criteria: The product specifications and acceptance/rejection criteria, such as acceptable quality limit and unacceptable quality limit, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units). (FDA 21 CFR 210.3)

Acceptable Carryover Quantity (ACQ):  The ACQ is the potential maximum allowable quantity of the previous product, which may be carried over to any subsequent product during manufacture.

The maximum allowable quantity of a guiding substance that can be carried over into subsequent manufacture. The guiding substance is generally the contaminant within the equipment train.

Accuracy: The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found. This is sometimes termed trueness. (ICH Q2). The degree of closeness of the determined value to the nominal or known true value under prescribed conditions. This is sometimes termed trueness.

The accuracy of an analytical method is the closeness of test results obtained by that method to the true value. Accuracy can often be expressed as percent recovery by the assay of known, added amounts of analyte. Accuracy is a measure of the exactness of the analytical method.

          % Accuracy = (Xbar – Target / Target) * 100

Action limit: Established criteria, requiring immediate follow-up and corrective action if exceeded. 

Active pharmaceutical ingredient: Any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect. (FDA 21 CFR 210.3)

Actual yield: The quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product. (FDA 21 CFR 210.3).

Adjustment:  The adjustment of an instrument to improve accuracy so it shows the correct value. It is recommended to calibrate before and after adjustment. See also calibration.

Adverse Event (AE): The development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. 

An undesirable medical condition can be symptoms (e.g. nausea, chest pain), signs (e.g. tachycardia, enlarged liver) or the abnormal results of an investigation (e.g. laboratory findings, electrocardiogram). In clinical studies an AE can include an undesirable medical condition occurring at any time, including run-in or wash-out periods, even if no study treatment has been administered. An adverse event can also be failure of expected pharmacological action.

Aerobes: An organism that requires (for growth) a level of oxygen equal to, or greater than that present in the atmosphere.

Air changes: The frequency (minutes, hours, etc.) with which the air in a controlled environment (classified area) is replaced. The air can be recirculated partially or totally replaced.

Air classifications: Classification of processing rooms or areas based on the allowed number of particles per cubic foot of air (USA) e.g. class 100, or particles per cubic meter (EU) depending on level of activity in the processing room. The EU refers to these air classifications as Grades A through D, with A being the cleanest during normal activity.

Air diffuser:  A plate in the ceiling where the air is forced through.  A diffuser may direct the air throughout the room

Air handling unit (AHU):  An integrated piece of equipment consisting of fans, heating and cooling coils, air-control dampers, filters and silencers.

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

Alert levels (environmental monitoring): established static and operational microbial or particulate levels giving early warning of potential drift from normal operating conditions which are not necessarily grounds for definitive corrective action but which require follow-up investigation.

Alert levels (media fill): an established number of media filled units which indicate the presence of microbial growth (e.g. positive units). The cause of the growth should be investigated, but is not necessarily a reason for definitive corrective action.

Alert limit: Established criteria giving early warning of potential drift from normal conditions which are not necessarily grounds for definitive corrective action but which require follow-up investigation. 

Air samplers: A calibrated piece of equipment that samples air by impacting a calculated amount of air onto a solid or semi-solid microbial growth media over a specified period of time. These samplers are used to determine the viable (microbiological) content of the air in the processing room. Some accepted samplers are Slit-To-Agar (STA) samplers, Centrifugal Samplers (CS), and Sieve Microbial Atrium (SMA) samplers.

Algae: Any member of a heterogeneous group of eucaryotic (cells that possess a definitive or true nucleus), photosynthetic, and unicellular or multicellular organisms. 

Anaerobes: An organism that does not use oxygen to obtain energy and cannot grow in an air atmosphere and for which oxygen is toxic.

Analyte: A specific chemical moiety being measured, which can be intact drug, biomolecule or its derivative, metabolite, and/or degradation product in a biologic matrix. 

Analytical run (or batch): A complete set of analytical and study samples with appropriate number of standards and QCs for their validation. Several runs (or batches) may be completed in one day, or one run (or batch) may take several days to complete. 

Analytical Procedure: The analytical procedure refers to the way of performing the analysis. It should describe in detail the steps necessary to perform each analytical test. This may include but is not limited to: the sample, the reference standard and the reagents preparations, use of the apparatus, generation of the calibration curve, use of the formulae for the calculation, etc. (ICH Q2).

Analytical Method Validation:  The process by which it is established, by laboratory studies, that the performance characteristics of the analytical methods meet the requirements for the intended application.

Annual Product Review (APR):  An evaluation, conducted at least annually, to assess the quality standard of each drug product with the objective of verifying the consistency of existing processes and the appropriateness of current specifications, and highlighting any trends, in order to determine the need for changes in drug product specifications or manufacturing or control procedures.

Ancillary system: A system that is not directly part of the equipment undergoing qualification. An example is a compressed air system that may be used in packaging to remove dust and other contaminants.

API – Active Pharmaceutical Ingredient:  Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product 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.

API Intermediate (INT):  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.

API starting material (Contributory Raw Material):  A raw material, intermediate, or API that is used in the production of an API, which 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 agreements, or produced in-house.

API packaging material: Any material intended for protect an intermediate or API during storage and transport.

Artwork:  A combination of a physical pack design, graphic design and approved text which gives a complete definition for printing of a package component.

“As-built” drawings: Drawings of the equipment, indicating utilities etc. placement of equipment components, completed as the equipment was being built or manufactured.

“As is “drawings: Drawings of the equipment as it has been placed/modified within the final location.

As found: The condition or status of equipment, instrumentation or systems prior to calibration or maintenance activities.

As left:  The condition or status of equipment, instrumentation or systems following calibration or maintenance activities.

Asepsis: Prevention of microbial contamination of living tissues or sterile materials by killing, removing or excluding spores.

Aseptic filling:  A process by which the drug or biological product, container, and closure are sterilized separately then assembled under strict environmental conditions.

Authorized person: Person recognized by the authority as having the necessary basic scientific and technical background and experience.

Audit:  Note that, audits may assess: systems, processes, procedures, facilities, products, studies, reports, records, and/or data for compliance with policies, standards, procedures, guidelines, regulations, or regulatory submissions. Audits may assess both in-house and external activities. Audits may be planned, or undertaken on a ‘for-cause’ basis.

Auditee: The firm that is being audited.

Automated System:  Includes (but is not limited to) automated manufacturing equipment, process control systems, automated laboratory systems, manufacturing execution systems, and, manufacturing and laboratory database systems.  The automated system consists of the hardware, software, and if applicable, network components, together with the controlled functions and associated documentation.

Note:  Automated systems are a type of computerized system.

Atypical result: See out-of-trend (OOT) result.

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B.

 

Bacteria: A class of microscopic single cell organisms containing nuclear material within the cell wall (and not within a distinct nucleus, as for fungi). They can be found in almost every imaginable environment on the planet.

Batch (or lot): 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 21 CFR 210.3) 

A defined quantity of starting material, packaging material or product processed in one process or series of processes so that it could be expected to be homogeneous.

Note: To complete certain stages of manufacture, it may be necessary to divide a batch into a number of subbatches, which are later brought together to form a final homogeneous batch. In the case of continuous manufacture, the batch must correspond to a defined fraction of the production, characterised by its intended homogeneity.

For the control of the finished product, a batch of a medicinal products comprises all the units of a pharmaceutical form which are made from the same initial mass of material and have undergone a single series of manufacturing operations or a single sterilisation operation or, in the case of a continuous production process, all the units manufactured in a given period of time. (PIC/S).

Batch number (or lot number): A specific quantity or lot of a test or control article that has been characterized according to Sec. 58.105(a). (From FDA CFR 58).

A distinctive combination of numbers and/or letters which specifically identifies a batch.

Batch Production record:  The document used for each individual batch of API, based on the master production instruction.

Beta-Lactams:  A major class of antibiotics that includes pencillins, cephalosporins and carbapenems.

Bias: An effect which deprives a statistical result of representativeness by systematically distorting its accuracy, as distinct from a random error which may distort in one action but balances out on the average.

Bias of Estimate: The deviation of the expectation of an estimate of a parameter from the true value of the parameter.

Binary fission: The process whereby a single cell divides to form two cells of equal size.

Bioburden: The number of micro-organisms that an object is contaminated with.

Biocidal: Action which kills micro-organisms (irreversible).

Biological contamination: Refers to contamination by bacteria, yeasts, moulds, viruses, or any other micro-organisms that may be present in product. 

Biological agents: Microorganisms, including genetically engineered microorganisms, cell cultures and endoparasites, whether pathogenic or not. 

Biological matrix: A discrete material of biological origin that can be sampled and processed in a reproducible manner. Examples are blood, serum, plasma, urine, feces, saliva, sputum, and various discrete tissues. 

Biological Indicator (BI):  A BI is a characterized preparation of a specific microorganism that provides a defined and stable resistance to a specific sterilization process.

Biostatic: Action which inhibits growth (reversible on the removal of the biostatic agent from the organisms).

Binder: A chemical that acts to hold granules in a tablet together.

Blank sample: A sample of a biological matrix to which no analytes have been added that is used to assess the specificity of the bioanalytical method.

Blending:  The process of combining materials, each within the same specification, to produce a homogeneous intermediate or API.

Blender discharge: The processed material that is removed from the blender after the processing operation has been completed.

Bracketing: The design of a stability schedule such that only samples on the extremes of certain design factors (for example, strength, package size) are tested at all time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. Where a range of strengths is to be tested, bracketing is applicable if the strengths are identical or very closely related in composition (for example, a tablet range made with different compression weights of a similar basic granulation, or a capsule range made by filling different plug fill weights of the same basic composition into different size capsule shells). Bracketing can be applied to different container sizes or different fills in the same container closure system.

Bulk Formulated Product:  A pharmaceutical product (Formulated Drug/Formulated Product) is held in large intermediate or shipping containers and ready to be filled into primary containers.

Bulk Intermediate: A material produced during steps of the processing of a Drug Substance/API, which must undergo further molecular change or purification before it becomes a Drug Substance/API.

Bulk product: Any product which has completed all processing stages up to, but not including, final packaging.

Bulk production batch:  A batch of product, of a size described in the application for a Marketing Authorization, either ready for assembly into final containers or in individual containers ready for assembly to final packs. (A bulk production batch may, for example, consist of a bulk quantity of liquid product, of solid dosage forms such as tablets or capsules, or of filled ampoules.)

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C.

Calibration: The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard. 
Comparison of a measurement standard or instrument of known accuracy with another standard or instrument to detect, correlate, report or eliminate by adjustment any variation in the accuracy of the item being compared with the standard traceable to a Recognized National Standard.
 
Calibration standard: A biological matrix to which a known amount of analyte has been added or spiked . Calibration standards are used to construct calibration curves from which the concentrations of analytes in QCs and in unknown study samples are determined. (Source: Guidance for Industry Bioanalytical Method Validation 2001- CDER)
 
Capable process: A process that performs within specification limits. 
 
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 (fully characterised for identity and absence of contamination). 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.
 
Cell wall structure: Another way to classify bacteria is based on their cellular structure. They can be either Gram-positive (blue) or Gram-negative (red) depending on how they react when stained with Gram Stain. Gram Stain is a differential stain by which bacteria are classified depending on whether they retain or lose the primary stain when treated with a decolorizing agent.
 
Centrifugation: A method of separating a solid/liquid mixture by rotating it at high speed in a cylindrical container. The solid will remain on the sides (through centrifugal force) while the liquid goes to drain.
 
Certificate of Analysis: A document describing the quality and purity data from QC testing of a particular lot or batch. 
 
A batch-specific document issued by a manufacturer, vendor, or exporter that contains all of the information given on a Certificate of Manufacture (C of M) but in addition also has the analytical results and specification limits for the referenced batch.
 
Certificate of Analysis for Mutual Recognition Agreements (MRA): A batch-specific document issued by the fabricator/manufacturer in the exporting country to accompany batches transferred between countries having an MRA in force with one another.
 
This certificate attests that the batch meets the specifications and has been produced in accordance with the requirements of the Regulatory Authority approval and with cGMP.  In addition to the clauses required for a standard C of A it also contains references to the importing country and the Manufacturing and Marketing Authorizations.
 

Certificate of Manufacture (C of M): A batch-specific document issued by a manufacturer, vendor, or exporter attests that the batch meets the specifications and has been produced in accordance with the requirements of the Regulatory Authority approval and with cGMP.

Certification: Is the act of approving (accepting) quality control results provided by the supplier in relation to a specific material, thereby eliminating the need to undertake some or all laboratory tests on receipt of that material at gmp site unless specifically required to meet regional/local GMP and/or import regulations.

Certification of a finished product batch: The certification, in a register or equivalent document by a QP, as defined in Article 51 of Directive 2001/83/EC before a batch is released for sale or distribution.

Certified materials: A certified material is a material provided to receiving site, by a supplier, that is released by a sister site, or released by a contractor directly into the site’s distribution chain, without repeat laboratory testing by the receiving site or an independent laboratory approved by the receiving site, unless such testing is necessary to meet cGMP requirements, e.g. identity testing and/or local import regulations.

A certified material may undergo additional laboratory testing by the receiving site, or an independent laboratory approved by the site if the supplier does not perform all tests required to release the material.

Certification Report: A compilation of all information gathered by the Receiving Site Supplier Certification Team supporting the award/re-assignment of certification status.

Change control: A formal monitoring system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validation status of a system or process and cause corrective action, if any, to be taken that will ensure that the system or process retains, or is placed back into a validated state of control.
 
Change Request: This is a collective name for a ‘Request for Change’ form 
 
Chemical contamination: Occurs when product becomes contaminated with other materials or products. 
 
Chromatography: The science which studies the separation of molecules based on differences in their structure and/or composition. Chromatography is also a method to separate components of an analyte involving a mobile phase moving through a stationary phase. Types of chromatography are thin layer chromatography, gas chromatography, liquid chromatography and paper chromatography.
a. Gas chromatography (GC): 
A type of chromatography where a liquid sample is vaporized and then injected into a column on a carrier gas. Components of the analyte bind to the 
column at different rates, with different parts of the analyte passing through the column at different times.
b. High performance liquid chromatography (HPLC): 
A type of chromatography using relatively high pressures and small diameter column packings to achieve sharp and highly reproducible elution profiles.
 
Chromatogram: The record of results for the process of chromatography that shows the response of each component as a function of time and concentration of the sample. The record may be the media itself, e.g. the paper or thin layer medium, a piece of paper (e.g. computer print out) or it may be retained in a computer and displayed on video display terminal.
 

Classified Areas: Pharmaceutical facility areas that require validated and controlled environmental air systems.

Clean area: An area with defined environmental control of particulate and microbial contamination constructed and used in such a way as to reduce the introduction, generation and retention of contaminants within the area. Note: The different degrees of environmental control are defined in the Supplementary Guidelines for the Manufacture of sterile medicinal products. 
 
Clean/contained area: An area constructed and operated in such a manner that will achieve the aims of both a clean area and a contained area at the same time.
 
Cleaning: The removal of visible and microscopic contamination by dirt, extraneous matter, or product residues, by mechanical or physical means. Cleaning is usually followed by visual inspection to determine the effectiveness of the cleaning operation.
 
Clean-In-Place (CIP): An automated cleaning process that relies on both chemical removal and physical agitation.
 

Clean (Pure) Steam: High quality steam produced from purified water (or better) with a distribution system constructed of non-rusting materials and used in applications that may directly contact product contact surfaces. 

Climatic zones: The four zones in the world that are distinguished by their characteristic, prevalent annual climatic conditions. This is based on the concept described by W. Grimm (Drugs made in Germany, 28:196-202, 1985 and 29:39-47, 1986).
 

Clinical Trial Application (CTA): An application to regulatory authority(ies) for the permission to perform a clinical study using an investigational product in subject/patients. Defined in ICH guideline for GCP, May 1996.

Cleaning Process Establishment: Cleaning carried out to establish an effective cleaning method for API or intermediate prior to formal cleaning validation.

Cleaning Validation: Establishing documented evidence that a specified cleaning procedure will provide a high degree of assurance that it can be used to consistently clean a piece of equipment or a facility to a predetermined acceptable level of cleanliness.

Close out meeting/exit meeting/closing meeting: The last formal meeting held between the auditee and the auditor(s) before the auditors leave the firm.
 
Coefficient of variation (cv): The ratio of the standard deviation to the absolute value of the arithmetic mean. (Usually expressed as a percentage) Otherwise expressed as the relative standard deviation or RSD.
 
Cold storage: Refers to the storage of products requiring a storage temperature of 2oC-8oC, or requiring to be stored frozen. 
 
Colony forming unit (cfu): A microbiological term that describes the formation of a single macroscopic colony after the introduction of one or more microorganisms to microbiological growth media. One colony forming unit is expressed as 1 CFU.
 

Commissioning: The process of verification that new or modified assets can meet their design intent, while bringing them from a constructed state into beneficial operation, as defined by the acceptance criteria and agreed with the Project Sponsor.

An engineering term that covers all aspects of bringing a system or sub-system to a position where it is regarded as being ready for use in pharmaceutical (and other) manufacture. Commissioning involves all the basic requirements of Installation Qualification and Operational Qualification. (FDA Guidance: Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice)
 
Common equipment: Equipment used for more than one type of product. 
 
Commitment batches: Production batches of a drug substance or drug product for which the stability studies are initiated or completed post-approval through a commitment made in the registration application.
 

Compendial Water: Water covered by a compendial monograph. It contains no added substances. 

Complaint: A complaint is any expression of dissatisfaction with a product or service marketed.
 
a. Critical Complaint:
A complaint that strongly indicates the purity, identity, safety or efficacy of a product may have been compromised and has the potential to cause a life threatening or serious health situation.
 
b. Serious Complaint:
A complaint that indicates the purity, identity, safety or efficacy of a product may have been compromised, but does not present as a life threatening or serious health risk.
 
 c. Standard Complaint:
A complaint that is neither critical nor serious.
 d. Justified Complaint:
A complaint where the investigation has shown the complaint to be valid and that it occurred under company control.
 
e. Non-Justified Complaint:
A complaint where the investigation has shown no valid reason for the complaint.
 
Components: FDA defines this as any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product. The equivalent word in EU would be starting material. In this module the word component is used. The words are used interchangeably, depending on the stage of production, with a number of different terms such as: material, intermediate bulk, active pharmaceutical ingredient, excipient, starting material, raw material, goods.
 
Compounding: A process in which one bulk drug substance is combined with another bulk drug substance and/or one or more excipients to produce a drug product.
 
Computer: Hardware components and associated software designed to perform specific functions.
 
Computerized process: A process where some or all actions are controlled by a computer. (FDA Guidance: Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice)
 
Computerized system: A system including the input of data, electronic processing and the output of information to be used either for reporting or automatic control. . (From: PIC/S cGMP.).
 

Computerized System Validation: Establishing documented evidence which provides a high degree of assurance that a computerized system will consistently function in accordance with its pre-determined specifications and quality attributes throughout it’s lifecycle.  (It applies to systems which can affect product quality.)

Concurrent Validation: The validation carried out during routine production of products for sale. (In exceptional circumstances it may not be acceptable to complete a validation program before routine production starts.)

Confirmation: An internal Certificate of Analysis or Certificate of Manufacture will be issued that confirms a process or test has been conducted in accordance with GMP and the relevant Marketing Authorization, as agreed in writing (QA Agreement) with the QP responsible for certifying the finished product batch before release. 

Consistency: The ability of the instrument to test the same sample numerous times under the same conditions and generate the same data within in a very strict range.
 

Consumable: A consumable is a material or item of disposable equipment used in the manufacture of an API or finished product that is not a process chemical (solvent), API raw material/intermediate, excipient or packaging material. Examples are filters, and disposable tubing used in the manufacturing process. A GMP critical consumable is defined as where failure to specify and control quality requirements could adversely affect product quality/patient safety.

Container closure system: The sum of packaging components that contain and protect the dosage form. This includes primary packaging components and secondary packaging components (the latter are intended to provide additional protection to the drug product). A packaging system is equivalent to a container closure system.
 

Containment: The action of confining a chemical entity within a defined space.

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

ii. Secondary containment: A system of containment, which prevents the escape of a chemical entity from a system of primary containment into the external environment or into other working areas.  It involves the use of localized extract booths or rooms with specially designed air handling, the existence of airlocks and secure operating procedures.  In many cases it may add to the effectiveness of primary containment.

Contact plates: Usually a plastic plate that has a raised surface composed of microbiological solid media. The media is then pressed or rolled upon a surface, transferring the content of the surface to the media. RODACs (Replicate Organism Direct Agar Contact) plates are one example.
 
Containment: The action of confining a biological agent or other entity within a defined space. 
 
a. 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. 
 
b. 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 sterilizes for the exit of materials and secure operating 
procedures. In many cases it may add to the effectiveness of primary containment. 
 
Contained area: An area constructed and operated in such a manner (and equipped with appropriate air handling and filtration) so as to prevent contamination of the external environment by biological agents from within the area. 
 
Contamination: Refers to the presence of any foreign substance in a product, be it physical (e.g. foreign objects), chemical (e.g. degradation products), or microbiological (e.g. bacteria). 
 
Continuous monitoring: Ongoing sampling of environmental conditions throughout the period of operations, ensuring that update of data occurs constantly.
 
Contractor/Contract Operations: Provides a product/service to sponsoring organization (i.e. laboratory testing, producing an intermediate product and producing a finished product), that it cannot provide to other companies (e.g. making/packing products on which a firm owns the intellectual property).
 

Contract Acceptor (“ACCEPTOR”): A person or entity who agrees to provide the contract giver with a service, product, project or study according to the givers specified requirements.

Contract Giver (“GIVER”): A person or entity who on behalf of the site, commissions a service, product, project or study. 

Contributory raw materials: A raw material used in the production of an API that contributes to the final molecular structure of an API.
 
Control article: Control article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any article other than a test article, feed, or water that is administered to the test system in the course of a nonclinical laboratory study for the purpose of establishing a basis for comparison with the test article. 
 
Control chart: A statistical tool used to determine if a process performs within specification limits. 
 
Controlled environment: Any area in an aseptic process system for which airborne particulate and microorganism levels are controlled to specific levels that are appropriate to the activities conducted within that environment.
 
Control number: (see Lot number) 
 
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.
 
Controlled document: A controlled document is one which is maintained in such a way as to prevent or track changes which are made to it, is it signed and dated and retained in the QA files.
 
Correction: Correction refers to repair, rework or adjustment and relates to the disposition of an existing non-conformity, defect, or other undesirable situation 
 
Corrective Action: Action to eliminate the causes of an existing non-conformity, defect or other undesirable situation in order to prevent recurrence.
 
Counterfeit product: A product that looks identical to an original product both in drug appearance and packaging, but does not contain any active ingredients.
 

Critical:  A process step, process condition, test requirement or any other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification.

Critical Activity: An activity that will prevent the Active Pharmaceutical Ingredient or intermediate from meeting its specification when omitted or carried out incorrectly.

Critical Effect: This is the first significant adverse effect(s), which occurs as the dose increases from zero.  It is determined after consideration of all the available data.  For pharmacologically active compounds, the critical effect may be the pharmacological effect but this is not necessarily the case.

Critical Observation: “Deficiencies with Company Standards, and/or current regulatory expectations that provide immediate and significant risk to product quality, patient safety or data integrity, or a combination/repetition of major deficiencies that indicate a critical failure of systems.” Immediate corrective action and reporting to Management is required.

Critical Parameter: A process parameter that must be controlled within an established range to ensure that the Active Pharmaceutical Ingredient or intermediate will meet specification.

Crystallization: The formation of pure to nearly pure crystals of small or big molecules. Often used to purify a substance; crystallization of proteins is used to obtain their three-dimensional structure by x-ray analysis. 

Critical control points: Particular areas in a process that, if not controlled, can affect product quality. In-process checks should be carried out here. Critical processing parameters defines the operating conditions under which production has been validated to work. 
 
Critical item: Items which have been assessed to impact on product quality, safety and efficacy or otherwise present an unacceptable hazard if the equipment or its protective system should fail and where failure or malfunction could lead to danger to life, significant harm to any person or to the environment.
 

Critical Process Parameters: A process step, process condition, or any other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification. The requirements or specifications of an API or API process that can be measured and controlled to produce the desired quality of the API.

Critical Site: A surface in contact with a product from which possible contamination may find its way into an individual dose or packaging unit.  An example is a filling needle.
 
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 the process.
 
Critical quality attributes: Attributes the product is being specifically checked for when taking samples from the line. 
 
A characteristic of the API that contributes to its quality and is evaluated in terms of whether it does or does not exist, with respect to a given requirement
 
Cross contamination: Contamination of a starting material or of a product with another material or product. 
 
Cryogenic vessel: A container designed to contain liquefied gas at extremely low temperature.
 
Cs Observations”: A list of observations, based on the GMP regulations, generated by the FDA during a plant inspection and given to management at the closing meeting. The observations are known as Cs” because the form that is used to record the observations is Form Number 483.
 

Cytotoxic: A substance that kills or damages cells if the exposure is high enough.

240 SOPs, 197 GMP Manuals, 64 Templates, 30 Training modules, 167 Forms. Additional documents included each month. All written and updated by GMP experts. Checkout sample previews. Access to exclusive content for an affordable fee.

D. E. F.

D value: The time in minutes at a specific temperature required to reduce a surviving microbial population by 90%, i.e. a one-logarithm reduction.

Dead legs: An engineering term referring to a length of pipe, usually at right angles to the main pipe, that does not allow full flushing of the pipe to remove its contents. With a deadleg system residues or cleaning agents can remain in the “dead” area after the cleaning is completed. 
 
Dead spots: Lengths of piping where water stays and does not move.
 

De-certification: Is the act of reverting back to full or partially increased testing of a specific material on its receipt from the supplier.

De-certified material: A de-certified material is a material that has had its ‘certified’ status revoked.

Dedicated equipment: Used to manufacture only one type of product, or for a run of batches (a campaign) of the same formulation.

For the purpose of cleaning, equipment/plant shall be considered dedicated when it is used for the production of one API or intermediate and the potential for cross contamination does not exist. 

Defined media characteristics: When acid is produced, the resulting change in pH may cause the media to change color. This color change can aid in the identification of organisms.
 

Design Qualification: Documented verification that the proposed design of the facilities, equipment, or systems is suitable for the in-tended purpose.

Detection limit: The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value. This is considered to be 3 times the signal to noise ratio, within PAR&D.
 
Deviation: A deviation is a departure from standard procedures or specifications resulting in non-conforming material &/or processes, or where there have been unusual or unexplained events which have the potential to impact on product quality, system integrity or personal safety.  
 
a. Planned Deviation:
A deviation or change to test methods, laboratory or manufacturing procedures that has been planned and approved as part of temporary change.
 
b. Unplanned Deviation:
A deviation or change to test methods, laboratory or manufacturing procedures that was unplanned and was the result of an incident or error.
 
c. Critical deviation:
Deviation from Company Standards, and/or current regulatory expectations that provide immediate and significant risk to product quality, patient safety or data integrity, or a combination /repetition of major deficiencies that indicate a critical failure of systems
 
d. Serious deviation:
Deviation from Company Standards and/or current regulatory expectations that provide a potentially significant risk to product quality, patient safety or data integrity, or could potentially result in significant observations from a regulatory agency, or a combination /repetition of “other” deficiencies that indicate a failure of system(s).”
 
e. Standard deviation:
Observations of a less serious or isolated nature that are not deemed Critical or Major, but require correction, or suggestions given on how to improve systems or procedures that may be compliant, but would benefit from improvement (e.g. incorrect data entry).
 
Detection Limit (ICH Q2): The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value.
 

Direct Impact System / Component: This is a system / component that is expected to have a direct impact on product quality.  These systems / components are subject to qualification.

In some instances, Direct Impact Systems / Components will depend on Indirect Impact Systems / Components for effective operation and therefore, any interfaces need to be carefully assessed. 

Disinfectant: A substance or preparation represented to be capable of killing pathogenic or food spoilage micro-organisms, excluding those for internal use, antiseptics and food additives. Note: A disinfectant is not necessarily expected to kill spores or viruses. A disinfectant is not expected to necessarily achieve sterility.
 
Dispense:  To remove a specific quantity of material from the primary material and portion into the individual secondary container for charging to a batch or prescription.
 
Must pass the Disinfectant Test: Disinfectants must kill the organisms in 10 minutes or less.
 
Dosage form: A pharmaceutical product type, for example tablet, capsule, solution, or cream. It usually contains a drug substance in association with excipients, but not always.
 
Due diligence audits: Audits performed to evaluate if an external organization identified for in-licensing, acquisition, or collaboration is fit for purpose.
 
Drug product: 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 21 CFR 210.3) 
 
Drug substance: The unformulated drug substance that may subsequently be formulated with excipients to produce the dosage form.
 

Dynamic / “in-operation” testing:  Testing performed during processing operations or within an active shift (as applicable) with personnel present to confirm that the environment remains under control during these conditions. 

Elution: The process during a chromatography run by which purified product is extracted from a column. 
 

Endotoxins: Toxic molecules consisting of lipopolysaccharide originating from the outer cell wall of Gram-negative bacteria. Endotoxins may cause fever reactions in humans.

Endotoxin-Controlled Purified Water: Water that, as a minimum, meets the requirements of Purified Water with the addition of the Bacterial Endotoxin Test.

Endotoxin test: A test designed to determine if there are fever producing substances in the drug product. This substance can be produced by the degradation of gram negative bacteria from their cell walls. Endotoxin is harmful to humans.
 
Environmental monitoring program: A defined documented program which describes the routine particulate and microbiological monitoring of processing and manufacturing areas and includes a corrective action plan when action levels are exceeded. This program provides meaningful information on the quality of the aseptic processing environment when a given batch is being manufactured as well as environmental trends of the manufacturing area. An adequate program identifies potential routes of contamination, allowing for implementation of corrections before contamination occurs.
 

Equilibration Time: The period of time which elapses between the attainment of the sterilizing temperature in the chamber and the attainment of the sterilization temperature in all parts of the load. This period of time is an indication of the ability to properly remove air from the load items; consequently it should only be evaluated for heat penetration probes placed in porous loads.  It is not applicable to heat penetration measurements in liquid loads.

Equipment Train: All process equipment, including flexible hoses and pipe work, that is in direct contact with the product during manufacture of a specific product, e.g. granulation, drying, milling, mixing, compaction and coating. Used to identify the total surface area potentially at risk to cross-contaminate a product.  Disposable or dedicated product specific parts are excluded.

Excipient: Anything other than the drug substance in the dosage form.
 
Excursion: A testing result that deviates from normal expectations defined by the firm. 
 
Exotic organism: A biological agent where either the corresponding disease does not exist in a given country or geographical area, or where the disease is the subject of prophylactic measures or an eradication program undertaken in the given country or geographical area.
 
Expiry date (or Expiration Date): Indicates the date after which the goods cannot be guaranteed to be safe for use. 
 
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. Impurity: Any component present in the intermediate or API that is not the desired entity. (From: ICH Q7A – cGMPs for Active Pharmaceutical Ingredients).
 
Extraction: The removal of a chemical from a mixture by the use of a selective solvent.
 

F0: The time required at any given temperature between 100°C -140°C that is equivalent to the sterilization effect of steam at 121.1°C (250°F). Assumes a Z value of 10°C.

Factory Acceptance Testing (FAT): Pre-delivery equipment testing and inspection performed at the factory.
 
Facultative Anaerobe: An organism which does not require oxygen for growth but may use it if it is available. Grows well under both aerobic and anaerobic conditions.
 
FEFO (first-expiry, first-out): A warehouse principle whereby the first stock due to time-expire is the first stock picked for use.
 
FIFO (first-in, first-out): A warehouse principle whereby the first stock that arrives is the first stock picked for use.
 
Fermentation: A process in which an agent such as yeast, a bacterium, mold or enzyme causes an organic substance to break down into simpler substances.
 
Fertility: The ability to support micro-organisms that the media is claimed to support.
 
Filtration: The separation of a solid from a fluid by passing the liquid through a filter, cloth or other porous medium.
 
Finished product: A medicinal products which has undergone all stages of production, including packaging in its final container. 
 
Formal stability studies: Long-term and accelerated (and intermediate) studies undertaken on primary and/or commitment batches according to a prescribed stability protocol to establish or confirm the re-test period of a drug substance or the shelf life of a drug product.
 

For cause audit: An extraordinary audit focused to find the cause of a problem that is probably related to gaps/deficiencies in the quality system. It may be performed for critical issues or bad performance. It could affect the routine scheduled audit frequency.

Formulated Product: A finished dosage form, for example tablet, capsule, solution, suppository, that contains an API usually, but not necessarily, in association with inactive ingredients.  It also includes a finished dosage form used as a placebo.

Free From Gross Contamination: A state of cleanliness in which the equipment train may not be visibly clean but is free from any large quantities of material hold up.  The amount of solid/liquid remaining in the equipment is not quantified but is assessed by visual inspection (e.g., through a sight glass on a reactor).  Typically equipment is cleaned free from gross contamination through a single rinse and residual material is estimated at less than 5%.  

For pressure filters free from gross contamination normally requires the heel to be removed.

Freedom of information documents (FOI): Documents that you, as a citizen, can access from the FDA website. Included are warning letters issued by the FDA. This can provide you with information about current audit areas the FDA is interested in.
 

Functional Specification (FS): A document which records and approves the proposed solution to the User Requirement Specification prior to detailed design.

Fungi: Fungi are micro-organisms with a separate nucleus contained within a cell wall. Molds and yeasts are typical examples of fungi.

240 SOPs, 197 GMP Manuals, 64 Templates, 30 Training modules, 167 Forms. Additional documents included each month. All written and updated by GMP experts. Checkout sample previews. Access to exclusive content for an affordable fee.

G. H. I. J. K. L.

Gas chromatography (GC): A type of chromatography where a liquid sample is vaporized and then injected into a column on a carrier gas. Components of the analyte bind to the column at different rates, with different parts of the analyte passing through the column at different times.

Generation time: The time interval necessary for a cell to divide.
 
Good Distribution Practice (GDP): Refers specifically to practices related to the transport and distribution of product.
 
Goods Inward Number (GIN): See Unique Identifying Number (UIN). 
 
GMP: Good manufacturing practice.
 

GMP Documentation: GMP documentation is any procedure, control, record, distribution or related record, or electronic file that is required to be retained as evidence of compliance with GMP. 

GMP Master Document: An approved, version controlled GMP document is any policy, procedure, guideline, protocol, report, controlled form or template in paper or electronic form that is required for compliance with the GMP codes of practice and/or company Standards.

Good Engineering Practice: Established engineering methods and standards that are applied throughout the project lifecycle to deliver appropriate, cost-effective solutions

Good Warehousing Practice (GWP): Refers specifically to practices within the company warehouse. 
 
Goods Received Register: A register showing the receipt of starting materials. 
 
Gram Stain: Gram Stain is a differential stain by which bacteria are classified depending on whether they retain or lose the primary stain when treated with a decolorizing agent.
 
Grade A area:  The normal air classification for an aseptic processing area. This classification means that there are not more than 3,500 particles measuring 0.5µm or larger in one cubic meter of air, when measure during activity. Grade A may be considered equivalent ISO class 5 and FDA class 100. Other grades/requirements can be found in the EU-GMP.
 
Granule: A particle that has been mixed or blended to achieve a certain size, shape and composition. The act or process of forming or crystallizing into grains; as, the granulation of powder and sugar.
 
Granulation: The process of creating granules
 
Granulation (Dry): Modification of the powder morphology using dry compaction forces.
 
Granulation (Wet): Adding a liquid to a powder that causes particles to bind together through capillary forces.
 

Guiding Substance: The guiding substance is generally the contaminant within the equipment train that is considered to have the greatest potential impact on patient safety. This is assessed by taking into consideration information on toxicity, ease of removal and pharmacological activity. Often the guiding substance will be the final product from the equipment train, but it may be a reagent or intermediate in the synthesis if it is known to be highly toxic.

A guiding substance (or substances) should be selected such that verification of the removal of the guiding substance to an acceptable level will assure that any residual contamination from other materials in the contamination matrix is also below an acceptable level.

There may be a need to define more than one guiding substance if there is more than one potential contaminant with significant toxicological/pharmacological activity that is removed by a different cleaning method (e.g. a heavy metal from a catalyst may be considered as a guiding substance along with the final product from the equipment train).

Hazard (toxic): Any substance, which has the potential to cause harm to people.

Herbal medicinal products: Medicinal products containing, as active ingredients, exclusively plant material and/or vegetable drug preparations. 
 
Heel: An expression used for build-up of material in equipment used for continuous or campaign production leading to a risk of carry-over of contaminants (e.g. impurities or microorganisms). Examples of risks for significant carry-over between batches are filtration and micronisation.
 

HEPA filter: High efficiency particulate air filter with a minimum 0.3 micron particle retaining efficiency of 99. 97 percent.

Holding: Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products. (FDA 21 CFR 210.3).
 
High efficiency particulate air (HEPA) filter: Retentive matrix designed to remove a defined percentage of particulate matter of a defined size. Retentive matrix designed to remove a defined percentage of particulate matter of a defined size.
 

High performance liquid chromatography (HPLC): A type of chromatography using relatively high pressures and small diameter column packings to achieve sharp and highly reproducible elution profiles.

Highly Purified Water (HPW): Water produced from Potable Water by methods including, for example, double-pass reverse osmosis coupled with other suitable techniques such as ultrafiltration or deionization. HPW (Highly Purified Water) meets the same quality standards as WFI (Water for Injections) but the production methods are considered less reliable than distillation and thus it is considered unacceptable for use as WFI. The specification for HPW is defined in the European Pharmacopoeia (EP) and HPW is a consideration only for certain products supplied to the European Union (EU).
 

Hot Spot: A surface that is judged to be hard to clean or has the potential for hold up of materials. 

Housekeeping: Those activities designed to keep a facility in a clean, sanitary and well-maintained condition.
 

House Steam: Steam produced from potable, softened or deionized water with a distribution system made of iron or steel and treated with additives to minimize corrosion and only used in applications with non-product contact.

HVAC: Integrity test: a test to determine the functional performance of a filter or filter system and detect the presence of individual leaks in the filter media, frame, and seal.

Impurity: Any component present in the intermediate or API that is not the desired entity.
 
Impurity Profile: A description of the identified and unidentified impurities present in an API. 
 
Impermeable container: A container that provides a permanent barrier to the passage of gases or solvents. For example, sealed aluminum tubes for semi-solids, and sealed glass ampoules for solutions.
 
Inactive ingredient: Any component other than an active ingredient. (FDA 21 CFR 210.3)
 

Incident rates: The rate or frequency at which contamination is observed in an environment. Typically expressed as a percentage of samples in which contamination is observed per unit time.

Indirect Impact System / Component: This is a system / component that is not expected to have a direct impact on product quality, but typically will support a Direct Impact System / Component.

These systems / components are not subject to qualification, but are subject to Good Engineering Practice (GEP).

Infected: Contaminated with extraneous biological agents and therefore capable of spreading infection.
 
Inoculum: A small quantity of a microbiological organism transferred into a large volume of culture media to grow large quantities of the microbiological organism.
 
In-process control: Checks performed during production in order to monitor and if necessary to adjust the process to ensure that the product conforms to its specification. The control of the environment or equipment may also be regarded as a part of in-process control. 
 
In-process material: Any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product. (FDA 21 CFR 210.3).
 

Installation Qualification (IQ): Documented verification that all physical aspects of a facility or system, which affect product quality, adhere to the approved specification and are correctly installed. 

Integrity test: A test to determine the functional performance of a filter or filter system and detect the presence of individual leaks in the filter media, frame, and seal.
 
Intermediate: A material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (Note: this guidance only addresses those intermediates produced after the point that a company has defined as the point at which the production of the API begins.) 
 
Intermediate testing: Studies conducted at 30°C/65% RH and designed to moderately increase the rate of chemical degradation or physical changes for a drug substance or drug product intended to be stored long-term at 25°C.
 
Intermediate product: Partly processed material which must undergo further manufacturing steps before it becomes a bulk product. 
 
Internal standard: Test compound(s) (e.g. structurally similar analog, stable labeled compound) added to both calibration standards and samples at known and constant concentration to facilitate quantification of the target analyte(s).
 
Inventory: The list of equipment for a facility, organized in a convenient hierarchy, with equipment identified at the level at which the maintenance history will be documented and maintained.
 
Investigation: A formal and documented review of a deviation, issue, incident or problem, to identify its root cause and determine the actions required to address it.
 
Investigational Medicinal Product: A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including already with a marketing authorization but use 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.
 

Japanese New Drug Application (JNDA): Application to be submitted for regulatory drug approval to the Japanese Ministry of Health, Labor and Welfare (MHLW).

Known Laboratory Error: A laboratory test result that is attributable to an event or incident that is known to be caused by an instrument, environmental, analyst or other source that has an assignable cause. 
 
Laboratory Information Management System (LIMS): A system which can be used to schedule and record analytical data.
 
Laminar flow: An airflow moving in a single direction and in parallel layers at a constant velocity from the beginning to the end of a straight-line vector. However, true laminarity is not achievable in clean room applications. “Unidirectional flow” is the more accurate description for clean room applications and is defined as; an airflow moving in a single direction, in a robust and uniform manner and at sufficient speed to reproducibly sweep particles away from the critical processing or testing areas.
 

LD50 value: The LD50 (Lethal Dose, 50%) value is typically expressed in mg of material per kg of subject-body-weight, and indicates the quantity of material that, if administered to a population of subjects, will cause 50% of the subjects to perish.

Lead Audit Site: The site/function that is accountable for conducting quality audits of suppliers.

Level 1 Deviation: A deviation that may have an actual or potential adverse effect on product quality (inc. purity and identity) safety or efficacy.  Alternatively, a level 1 deviation may arise as a consequence of numerous repeated level 2 deviations.

Level 2 Deviation: An isolated event or deviation from an agreed/approved procedure or process that normally results in a rapid corrective action or establishment of such corrective actions. Alternatively, a level 2 deviation may arise as a consequence of numerous repeated level 3 deviations.

Level 3 Deviation: A deviation from GMP or procedure with no impact on product quality. 

Lead Site: The Lead Site is the site reflected in the Vendor and Contractor Database to be accountable for conducting specified material related QA activities. If no Quality Assurance Agreement Coordination site is assigned, the Lead Site would be responsible for GMP related interactions and issues, conducting audits, and development of the Quality Assurance Agreement.

Limit of detection (LOD): The lowest concentration of an analyte that the bioanalytical procedure can reliably differentiate from background noise.
 

Limit of Quantification: The lowest amount of a given substance in a sample that can be quantified with suitable accuracy and precision with the selected analysis procedure. 

Linearity (ICH Q2): The linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. (Source: Guideline for Industry Text on Validation of Analytical Procedures ICH-Q2A – March 1995)
 
Line clearance: Before starting a packaging and labelling operation, the line clearance includes cleaning the area and machines, removing all previous product and waste from the area and machines, and reconciling all printed material and product from the previous batch. See Line setup. 
 
Line setup: Before starting a packaging and labelling operation, separate to a “line clearance”, this involves verifying that the line has been cleared; assembling the materials needed for the new operation; verifying that each container of bulk material is approved for use; verifying that printed matter conforms to descriptions in the batch record; and labelling the line with the product name and strength.
 
Linearity:  The linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. For those analytical procedures which are not linear, another mathematical relationship (proportionality) must be demonstrated.
 

Local Exhaust/Extract System: Consists of a control exhaust hood, duct work, exhaust, filter and controls used to control an air contaminant by collecting it at source.  A local hood/booth is the point of entry of air to the system.

Long-term testing: Stability studies under the recommended storage conditions for the re-test period or shelf life proposed (or approved) for labeling.
 
Lot: 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 21 CFR 210.3).(see also Batch for PIC/S definition).
 
Lot number: Any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. (FDA 21 CFR 210.3)
 
A distinctive combination of numbers and/or letters which specifically identifies a batch. (PIC/S) 
 
Lower limit of quantification (LLOQ): The lowest amount of an analyte in a sample that can be quantitatively determined with suitable precision and accuracy. 

240 SOPs, 197 GMP Manuals, 64 Templates, 30 Training modules, 167 Forms. Additional documents included each month. All written and updated by GMP experts. Checkout sample previews. Access to exclusive content for an affordable fee.

M.N.O.

Major Observation: “Deficiencies with Company Standards and/or current regulatory expectations that provide a potentially significant risk to product quality, patient safety or data integrity, or could potentially result in significant observations from a regulatory agency, or a combination/repetition of “other” deficiencies that indicate a failure of system(s).”

Make ready: In the printing industry, this refers to the first few sheets or labels to pass through a printing machine before the actual run starts. Make ready materials should be discarded at each step in the run. 
 
Maintenance: The combination of all technical, administrative and managerial actions during the lifecycle of an item intended to retain it in or restore it to a state in which it can reliably perform a required function. Maintenance can be planned or unplanned.
 

Manometer: A device that measures the difference in pressure between two points.

Manufacture: All operations of purchase of materials and products, Production, Quality Control, release, storage, distribution of medicinal products and the related controls. (PIC/S)
 
Manufacturer: Holder of a manufacturing authorization.
 
Manufacturing formulae, Processing and Packaging Instructions: State all the starting materials used and lay down all processing and packaging operations.
 

Market Specific Requirements: These are the market specific requirements for the provision of BSD to customers and are held as an appendix to this guideline (Appendix VIII).  These requirements are for customers external to the company, they are not for internal Operations supply – when bulk finished products are shipped between Operations manufacturing sites for further processing CofA are always needed.

Marketing Authorization Application (MAA): Application for authorization to place medicinal products on market. This is a specific term for the EU/EAA markets.

Mass balance: The process of adding together the assay value and levels of degradation products to see how closely they add up to 100 percent of the initial value, with due consideration of the margin of analytical error.
 
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. 
 
Master production instruction: The approved process document or “recipe” that is used for preparing every batch of the intermediate and API.
 
Master seed lot: A culture of a micro-organism distributed from a single bulk into containers in a single operation in such a manner as to ensure uniformity, to prevent contamination and to ensure stability. A master seed lot in liquid form is usually stored at or below -70°C. A freeze-dried master seed lot is stored at a temperature known to ensure stability. Working seed lot: A culture of a micro-organism derived from the master seed lot and intended for use in production.
 

Material Safety Data Sheet (MSDS): A Material Safety Data Sheet provides information on the hazards to health, safety and environment inherent in a chemical substance.

Material: A general term used to denote raw materials (starting materials, reagents, solvents), process aids, intermediates, APIs, and packaging and labeling materials 
 
Material item code: An extra level of identification on a material’s label used in the Master Batch Record and formulation. This code also corresponds to the barcode, and usually helps identify the approved supplier and grade of the material.
 

Materials Validation: Provides documented evidence that all the necessary qualification associated with materials used during manufacture have been generated and approved as appropriate. It includes specifications, vendor audits/ vendor rating, purchase standards for Raw Materials and Excipients, Primary Packaging Materials, Processing Aids.

Matrixing: The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point. The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same container closure system, and, possibly in some cases, different container closure systems.
 
Matrix effect: The direct or indirect alteration or interference in response due to the presence of unintended analytes (for analysis) or other interfering substances in the sample. 
 

Maximum Daily Dose (MDD): The maximum dose of active substance (usually mg or g) typically administered to a patient in any 24hr period (e.g. as referenced in the Core Data Sheet).

Medical Device: Any instrument, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application, intended by the manufacturer to be used for human beings for the purposes of diagnosis, prevention, monitoring, treatment or alleviation of disease.

Medical Device Documentation: Medical Device Documentation is any procedure, control record, distribution or related record, or electronic file that is required to be retained as evidence of compliance to Medical Device Legislation.

Medicinal products: Any medicine or similar product intended for human use, which is subject to control under health legislation in the manufacturing or importing State.
 
Mean kinetic temperature: A single derived temperature that, if maintained over a defined period of time, affords the same thermal challenge to a drug substance or drug product as would be experienced over a range of both higher and lower temperatures for an equivalent defined period. The mean kinetic temperature is higher than the arithmetic mean temperature and takes into account the Arrhenius equation. When establishing the mean kinetic temperature for a defined period, the formula of J. D. Haynes (J. Pharm. Sci., 60:927-929, 1971) can be used.
 
Media: A substrate for growing microorganisms. If the tests are compendial tests, the type of growth media (e.g. trypticase soybean casein digest, blood, etc.) will be suggested. Different media are used to characterize different microorganisms based on nutritional requirements/preferences.
 
Media fills: A method of evaluating an aseptic process using a microbial growth medium. (Media fills are understood to be synonymous to simulated product fills, broth trials, broth fills etc. The term “process simulation” is sometimes used interchangeably with media fill).
 
Media growth promotion test: A test performed to demonstrate that microbial growth media will support microbial growth.
 
Method: A comprehensive description of all procedures used in sample analysis. (Source: Guidance for Industry Bioanalytical Method Validation 2001- CDER).
 

Method Validation: The process by which it is established, by laboratory studies, that the performance characteristics of the analytical methods meet the requirements for the intended application.

Microbial cultures: The growing of microorganisms, tissue cells, or other living matter in a specially prepared nutrient media.
 
Microbial limits testing: A test used to determine the quantity of organisms in a pharmaceutical raw material, in process sample, or finished sample and indicator organisms for a particular drug product.
 

Microbiological (BIO): Is a material from an animal or plant source that is used to grow and/or culture microorganisms and to monitor the production and quality assurance of sterile products (i.e. culture media).

Micro-organism selectivity: The ability of media to selectively support growth of specific organisms, whilst selectively inhibiting the growth of other micro-organisms.
 

Minimal Effect Dose (MED): The minimum dose at which  there is an observable pharmacological effect in man. Note: The MED is expressed as a weight of active substance (usually mg or g) per day.

Minimum Therapeutic Dose (MTD): The minimum amount of active substance typically given to a patient on each occasion as referenced in the Core Data Sheet. Note: The MTD differs to the MED when the lowest observable pharmacological effect is not the desired therapeutic effect.

Minor Observation: Observations of a less serious or isolated nature that are not deemed Critical or Major, but require correction, or suggestions given on how to improve systems or procedures that may be compliant, but would benefit from improvement (e.g. Good Practice seen elsewhere).

Mislabeling: Occurs when labelling and packaging information does not accurately reflect the contents of a container.
 

Mobile Equipment: Items of product contact equipment that are routinely disconnected and reconnected to plant to enable processing steps as part of an equipment train. This excludes small, easily inspected or disposable items and spares (e.g. sight glasses, small flexible lines, filter bags etc.).

Mold: A fungus characterized by a filamentous structure (mycelium).
 

Multi-Market Pack: A finished product pack that is designed for supply to two or more specified markets.

Multi-purpose Equipment/Plant: Non-dedicated plant or equipment used for the production of more than one intermediate or API where the potential for cross-contamination exists.

National Drug Code (NDC): Product identifiers for human drugs, which include a unique NDC number (US term).

Network Diagrams: A network diagram is a comprehensive, detailed view of the infrastructure. It should include both physical and logical components at a Local Area Network and Wide Area Network level. 

New Drug Application (NDA): Application to the US regulatory agency (FDA) to allow the sponsor to market a drug product in the US.

New molecular entities: An active pharmaceutical substance not previously contained in any drug product registered with the national or regional authority concerned. A new salt, ester, or non-covalent bond derivative of an approved drug substance is considered a new molecular entity for the purpose of stability testing under ICH Q1A(R2).
 
Negative room pressure: Pressures that contain dust within a room and prevent dust from getting into other rooms.
 

Nil Effect Dose (NED): Based on human data, is the maximum (single or repeated) dose at which there are no observable pharmacological effects in man.

No Observable Effect Level (NOEL): The dose level (usually mg or g) at which no toxicological effects are observed.

No Impact System / Component: This is a system / component that will not have any impact, either directly or indirectly, on product quality.  These systems / components are not subject to qualification, but are subject to Good Engineering Practice.

Non-Contributory Raw Material (NCRM): Is a raw material used in the production of an API that does not contribute to the final molecular structure of an API (e.g. catalyst, water/solvents that are dried off in process, cleaning fluids).

Nonclinical laboratory study: Nonclinical laboratory study means in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety. The term does not include studies utilizing human subjects or clinical studies or field trials in animals. The term does not include basic exploratory studies carried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics of a test article.
 
Non-Conformance: Means the non-fulfilment of a specified “material/product” requirement – (usually to a specification) A non-conformance usually leads to rejection or reworking of the item.
 

Non-Sterile Excipient : Is a material used to formulate API’s into pharmaceutical dosage forms suitable for administration to a patient. If sterile it is stored in a way that ensures its sterility for subsequent use in the preparation of a sterile formulated product that is not subjected to further aseptic or terminal sterilization.

Normal distribution: The distribution of a random continuous variable whose variability is due to the summed effect of many random independent causes. When plotted, this distribution has a single mode from which the curve falls away symmetrically on two sides, making the mode, median and mean all the one value.
 
Normal flora: Micro-organisms which normally inhabit a healthy human body or other natural environment.
 
Normal Operating Range: The normal operating limits of the instrument, equipment or system as required for operation within a process.
 
Objectionable organism: Micro-organisms which may present a health risk to consumers and which, for that reason, must be excluded from products. A microorganism that has been shown to cause harm to humans. Depending on the route of administration and the type of drug product, these organisms will be different for different products.
 

Occupational Exposure Limit (OEL): An in-house Occupational Exposure Limit (OEL) is a health-based exposure limit. This is the concentration of an airborne substance, averaged over a reference period, at which, according to current knowledge, there is no evidence that it is likely to be injurious to employees if they are exposed by inhalation, day after day.

Occupational Hygiene: Occupational hygiene practice is the application of principles to ensure adequate control of exposure to hazards and to minimize the risk in the workplace to adverse health effects.

Occupational Hygiene Monitoring (OHM): Occupational hygiene monitoring is the measurement of airborne substances in the workplace to assess potential for exposure and assess effectiveness of controls.

Online controls: GMP controls enacted during the packaging and labelling operation. Also called “in-process controls”. 
 

Operational Qualification (OQ): Documented verification that all functional aspects of a facility or system, which affect product quality, perform as intended throughout all anticipated operating ranges.

Operations Sites: Each Operations site/plant shall put in place validated cleaning procedures and generate data to confirm the validation of all product/equipment changeovers. 

Open-ended question: A question in which respondents are free to reply in their own words rather than being limited to choosing from among a set of alternatives. Example: How do you check in material coming into the plant site? An open-ended question is usually followed by a probing question to clarify or amplify information.

 

Opening meeting: A meeting is held between the auditee and auditors before the audit officially starts.

Opportunistic: A micro-organism that is not normally pathogenic, but which can cause disease if host defense mechanisms are decreased.
 
Oral solid: A dosage form taken by mouth that may include tablets, gelatin capsules, chewable tablets, or a form of sustained release delivery.
 
Oral solutions: A liquid dosage form taken by mouth containing an active drug product that is given to a patient. It may be a solution, elixir, or a suspension.
 
Out of Specification (OOS) Result: A finished product or raw material test result that falls outside approved, registered or official specifications or acceptance criteria. A validated OOS results in Non-conforming product.
 
Out of Trend (OOT) or Atypical Result: A result that is within specifications but is “atypical” or out of trend based on experience or systematic/statistical review of historical data. Typically OOT results would fall outside the alert limit but within the action limit.
 

Overkill cycle: A sterilization cycle that provides a 12-log reduction of a resistant Biological Indicator (BI) with a known D value of not less than 1 minute.  A typical cycle would provide a minimum of 15 minutes at or above 121.1°C.  This method is appropriate for heat stable products and processing equipment and is the preferred cycle type.

Overkill Sterilization Method: For steam sterilization, this approach is a cycle that provides a minimum 12-log reduction of a resistant Biological Indicator (BI) with a known D value of not less than 1 minute.

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P. Q.

 
pH: A symbol for the degree of acidity or alkalinity of a solution. The pH of the media is important because some bacteria will only grow well in a narrow pH range.
 
Packaging: All operations, including filling and labelling, which a bulk product has to undergo in order to become a finished product. 
Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being the filled, but not finally packaged, primary containers. (PIC/S)
 

Packaging Component – Critical (PCC): Is any printed packaging component, primary (product contact) component or device. Furthermore any secondary packaging component critical to the microbiological integrity, stability and/or administration of the product (e.g. aluminum pillow packs around semi-permeable).

Packaging Component – Non-Critical (PCNC): Is any non-printed or secondary (non-product contact) packaging component or device that does not fall within the definition of a PCC.

Packaging material: Any material employed in the packaging of a medicinal products, 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.
 

Packaging Site: A site where the particular medicinal product is packaged and/or labeled to produce ‘finished product’. A packaging site packing a product for a particular Marketing Company may be one of the following:

– a part of that Marketing Company organization

– a part of another contracted Marketing Company organization

– a company contracted to one of the above.

In the case of a larger Marketing Company that may have more than one packaging site in its organization, some of the responsibilities and activities identified in this Guideline may be discharged through a single group that acts for some or all these packaging sites.

Packing: Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products. (FDA 21 CFR 210.3).
 

Packing Bay: This is the area within a packing facility that houses the group of equipment that make up the packing line, e.g., blister former, labeler, and end of line equipment.

Packing Facility: The building and services which house the hardware.

Packing Line: The combination of equipment receiving the bulk formulated product and generating the primary container and may also generate the final pack for shipping.

Parameter: A quantity associated with a population. (See statistic).
 

Part Finished production batch: In the context of this procedure the term means the different stages of manufacturing required to formulate a product batch prior to it being in its final pack for release to the market. 

Particle size profile: The percentages of different sized particles that make up a passing granulation process
 
Parenteral: A pharmaceutical term used to describe a drug product that is sterile and delivered through injection/infusion.
 

Particle size profile: The percentages of different sized particles that make up a passing granulation process.

Particulate monitoring: Testing of the processing air for various sizes of viable and non-viable particles. Continuous monitoring is required in grade A and recommended for grade B by EU. FDA is less prescriptive and only state that such monitoring be frequent.
 
Passivation: The chemical treatment of stainless steel with a mild oxidant, such as a nitric acid solution, for the purpose of enhancing the spontaneous formation of the protective passive film. This process is designed to remove foreign metals, oxides, and corrosion from the surface of stainless steel and corrosion resistant steels, which allows water to move through the pipes and improves corrosion resistance.
 
Percentage of theoretical yield: The ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. (FDA 21 CFR 210.3).
 

Performance Qualification (PQ): A process which ensures /verifies that the facilities, utilities and equipment, as connected together, function as intended and produce intended results repeatedly and reliably.

Personal Protective Equipment (PPE): Any equipment worn by an operator or technician to minimize exposure to a drug or substance, e.g., to provide protection to hands, eyes, skin or to prevent inhalation.

Pilot scale batch: A batch of a drug substance or drug product manufactured by a procedure fully representative of and simulating that to be applied to a full production scale batch. For solid oral dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100,000 tablets or capsules, whichever is larger.
 

Piping and installation drawings: Mechanical drawing or blueprints of the required piping system for installation of equipment.

Positive room pressure: Pressures that exclude outside air from entering a facility. 
 
Potable Water: Water, that as a minimum, meets national standards for water intended for human consumption that have been documented as at least equivalent to World Health Organization (WHO) guidelines, the national standards for the USA, Europe and Japan meet or exceed the WHO guidelines. Potable Water is also known as Drinking Water.
 

Potent: A compound that is biologically active at low doses.

Precision (ICH Q2): The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
 
Precision should be investigated using homogeneous, authentic samples. However, if it is not possible to obtain a homogeneous sample it may be investigated using artificially prepared samples or a sample solution. The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements. 
 
a. Repeatability: 
Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision 
 
b. Intermediate precision: 
Intermediate precision expresses within laboratories variations: different days different analysts, different equipment, etc. 
 
c. Reproducibility: 
Reproducibility expresses the precision between laboratories (collaborative studies usually applied to standardization of methodology). 
The closeness of agreement (degree of scatter ) between a series of measurements obtained from multiple sampling of the same homogenous sample 
under the prescribed conditions.
 
Prescription drug: Any human drug required by Federal law or regulation to be dispensed only by a prescription, including finished dosage forms and active ingredients subject to section 503(b) of the Federal Food, Drug, and Cosmetic Act.
 

Pressure Regimes: A subdivision of a series of rooms into defined air pressure regimes.  The pressure regimes are cascaded, with the lowest pressure at the point of highest risk of loss of contaminant, to prevent airborne material transmission from process rooms into adjacent transit areas.

Pre-PAI audits/Mock-PAI: An audit performed by QA to determine if a site is prepared for a regulatory Pre Approval Inspection (PAI). This audit usually takes place prior to the submission of a regulatory filing.
 
Preventive action: Action taken to eliminate the cause of a potential non-conformity, defect, or other undesirable situation in order to prevent occurrence.
 
Preventive Maintenance System (PMS):  This system brings together people, equipment and procedures (including scheduled maintenance plans) to ensure that an asset is available for operation in accordance with its functional specification.
 
Primary batch: A batch of a drug substance or drug product used in a formal stability study, from which stability data is submitted in a registration application for the purpose of establishing a re-test period or shelf life, respectively. A primary batch of a drug substance should be at least a pilot scale batch. For a drug product, two of the three batches should be at least pilot scale batch, and the third batch can be smaller if it is representative with regard to the critical manufacturing steps. However, a primary batch may be a production batch.
 

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

Primary Packing: Any material employed in the packaging of a pharmaceutical product, excluding secondary packaging and any outer packaging used for transportation or shipment.  Primary packaging material(s) form the container/closure system for the product and therefore may be in direct contact with the product.  Examples include HDPE bottles/caps, blister strip packs, tubes/caps for ointments.

Primary Packing Equipment: The hardware used to put the product into its primary container, e.g., the blister former or bottle filler.

Primary reference standard: 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, (2) prepared by independent synthesis, (3) obtained from existing production material of high purity, or (4) prepared by further purification of existing production material. (From: ICH Q7A – cGMPs for Active Pharmaceutical Ingredients).
 
Printed matter: Includes labels for containers, package leaflets, labels for cartons or packaging, and printed containers. 
 

Printed Package Component: Printed packaging materials are printed and/or otherwise decorated packaging materials produced by a printer from an artwork. In the case of printed packaging components for finished products, the text, and in some cases the decoration, forms a part of the legal labelling and  design of the finished products, (e.g. labels, leaflets, pre-printed ampoules, tubes, foils).Some package components are printed during the packaging process. Such components fall within this definition. Printed components added to packs to meet transport, hazard and other distribution requirements are excluded.

Probability of a Non Sterile Unit / Sterility Assurance Level: The Probability of a Non Sterile Unit (PNSU) establishes the target for the lethal treatment. That target is the probability of not more than 1 contaminated unit in 1million units or the probability of less than one chance in a million that a viable organism remains following the sterilization process. The PNSU is expressed as1x10-6 and represents the minimum target for a sterilization process. Another term, Sterility Assurance Level (SAL) is often used and expressed interchangeably with PNSU i.e. SAL of 1×10-6.

Probing Question: A question used to clarify answers or discover more in-depth information. It is usually specific, focused and used after a general question has been asked. Example: You mentioned that you documented the arrival of raw materials, what do you record on that documentation?
 
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 products. (PIC/S).
 
Process Capability: A statistical indicator that measures how well a given process is running. It compares the actual variability in the process to the process specification.
 

Process Validation: Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.

Process Tolerance: The limits within which a process parameter should be maintained to ensure adequate product quality.
 
Processed: The final extract (prior to instrumental analysis) of a sample that has been subjected to various manipulations (e.g., extraction, dilution, concentration). 
 
Processing: Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products. (FDA 21 CFR 210.3)
 
Production: All operations involved in the preparation of a medicinal products, from receipt of materials, through processing and packaging, to its completion as a finished product. (PIC/S)
 
Production batch: A batch of a drug substance or drug product manufactured at production scale by using production equipment in a production facility as specified in the application.
 

Product Quality Complaint (PQC) Notification: Any report involving 1. The possible failure of a drug product to meet any of its specifications.  2. Non typical product characteristics: color, odor, embossing, labeling etc.  3. Dissatisfaction with the design of the product or the package or labeling.

Product Quality Review (PQR): Regular periodic review, normally conducted and documented annually, of an API, Bulk Formulated Product, Drug Product or Finished Product intended for the EU market or manufactured within EU but intended for export only, with the objective of verifying the consistency of existing process and the appropriateness of current specifications, to highlight any trends and to identify both product and process improvements.

For Bulk Formulated Product, Drug Product or Finished Product, the review includes verifying the appropriateness of current starting material specifications as well.

Product Specific Method: For steam sterilization, validation using this method relies on a thorough knowledge of the population and heat resistance of any product, items-to-be-sterilized, or environmental bioburden. The desired sterilization cycle lethality (Fvalue) as well as the attributes of the biological indicator used during validation are derived from knowledge of the bioburden population and resistance of the spore bioburden.

Prospective Validation: Establishing documented evidence that systems do what they purport to do prior to the commercial distribution of a new product or an existing product made by a new or modified process.

Protozoa: Protozoa are micro-organisms that have some animal characteristics – such as the way they ingest food.
 

Pure Steam: Pure Steam is produced using an appropriate steam generator, from Potable Water, usually pre-treated with an intermediate purification step(s). The steam condensate should meet the appropriate quality requirements of the water used in the facility.
Pure Steam is also known as Clean Steam or Pyrogen Free Steam.

Purified Water: Water produced by a suitable method (e.g., deionization, reverse osmosis, distillation, etc.) from potable water to meet specifications as defined by a compendial monograph.
 
Pyrogen: A substance that induces a febrile reaction in a patient. 
 
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.
 
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.  
 
a. Design Qualification: 
Documented verification that the proposed design of the facilities, equipment, or systems is suitable for the in-tended purpose.
 
b. Installation Qualification (IQ):
Provides evidence (documentation of tests) that the system has been installed correctly and safely, according to the manufacturers instructions 
and that installation can be repeated in support of disaster recovery. Also it ensures that the system work in accordance with established 
specifications 
 
c. Operational Qualification (OQ):
Provides documented evidence that functionality of the system meets the purchase specification requirements or performs as intended in its 
normal operating environment and range. 
 
d. Performance Qualification (PQ):
Provide documented evidence that the performance of the system under process conditions will consistently meet the specification and the 
products manufacturing process requirements. 
 
Qualification Audit (Retrospective Review): An audit carried out to confirm that a piece of equipment or a service has been satisfactorily qualified. This will be confirmed via a qualification audit checklist. 
 
Qualified Person (QP): EU requirement, a person who is held legally accountable for ensuring that all Quality conditions are met before releasing each batch of drug product.
 
Quality Assurance (QA): 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. 
 
A wide ranging concept which covers all matters which individually or collectively influence the quality of a product. It is the sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. (PIC/S, 1.2).
 
The activity of providing evidence that all the information necessary to determine that the product is fit for the intended use is gathered, evaluated and approved. The Quality Assurance department executes this function.
 
Quality assurance unit: Quality assurance unit means any person or organizational element, except the study director, designated by testing facility management to perform the duties relating to quality assurance of nonclinical laboratory studies. 
 
Quality Control (QC): Checking or testing that specifications are met. 
 
That part of Good Manufacturing Practice which is concerned with sampling procedure, specifications and testing, and with the organization, GMP documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory. (PIC/S, 1.4).
 
The activity of measuring process and product parameters for comparison with specified standards to assure that they are within predetermined limits and therefore, the product is acceptable for use. The Quality Control department executes this function.
 
Quality Control Unit: An organizational element with authority and responsibility as defined by 211.22.
 
Quality risk managementA systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.
 
Quality Unit(s): An organizational unit independent of production that fulfills both quality assurance and quality control responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization. 
 
Quantification range: The range of concentration, including ULOQ and LLOQ, that can be reliably and reproducibly quantified with accuracy and precision through the use of a concentration-response relationship. 
 
Quality standard: A set of minimum specifications and testing methods for raw materials, packaging components, chemical intermediates, active substance or drug products as established by official compendia and/or registered requirements.
 
Quantitation Limit (ICH Q2): The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products. 
 
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. (PIC/S)
 
Quarantine store: An area of the warehouse reserved for storing goods that have not yet been inspected or tested. 

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R.

 
Raw data: Raw data means any laboratory worksheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities of a nonclinical laboratory study and are necessary for the reconstruction and evaluation of the report of that study. In the event that exact transcripts of raw data have been prepared (e.g., tapes which have been transcribed verbatim, dated, and verified accurate by signature), the exact copy or exact transcript may be substituted for the original source as raw data. Raw data may include photographs, microfilm or microfiche copies, computer printouts, magnetic media, including dictated observations, and recorded data from automated instruments.
 
Raw Material: A general term used to denote starting materials, reagents, and solvents intended for use in the production of intermediates or APIs.
 
Range (ICH Q2): 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. 
 

Rapid Microbial Identity Test: A commercially prepared test that is able to identify microorganisms through interactions with chemicals within a matter of hours instead of days.

Reanalysis (New Initial Test): A test performed on the original sample (where possible) following invalidation of a test for a determinant error.
 
Real-time studies: Real-time studies are performed over the entire shelf life of the product, at temperatures and humidity in line with maximum storage claims. These studies are performed to give a confirmation of stability over the real shelf-life time.
 
Recall: A Major Quality Incident that leads to the removal of the entire affected batch or batches of material from the market or if clinical trials, from a study.
 
Recalled Goods store: An area of the warehouse reserved for isolating faulty or recalled goods, ensuring that they are not issued or sold by mistake. 
 
Reconciliation: A comparison, making due allowance for normal variation, between the amount of product or materials theoretically and actually produced or used. Record See Chapter 4 of the PICS cGMP.
 
A way of looking at material balance, focusing on losses or gains of materials. Reconciliation compares the amount of material going into a process with the amount coming out of the process.
 
Record: Provides a history of each batch of product, including its distribution, and also of all other relevant circumstances pertinent for the quality of the final product. (PIC/S, 4.1)
 
Recovery: The introduction of all or part of previous batches of the required quality into another batch at a defined stage of manufacture.
The extraction efficiency of an analytical process, reported as a percentage of the known amount of an analyte carried through the sample extraction and processing steps of the method.
 
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, (2) prepared by independent synthesis, (3) obtained from existing production material of high purity, or (4) prepared by further purification of existing production material.
 
Reference / reserve samples: Term used for samples taken for retention
 
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. (From: ICH Q7A – cGMPs for Active Pharmaceutical Ingredients)
 
Reject store: An area of the warehouse reserved for rejected batches.
 
Relative standard deviation (RSD): The internal correlation of the standard deviation of a set of specific numbers. The RSD is the sample SD divided by the sample Mean. The RSD is usually expressed as a percentage. The higher the percentage is, the worse the correlation. The RSD is also known as 100 times the Coefficient of Variation (CV).
 
Released store: An area of the warehouse reserved for batches or materials that have been tested and passed for use.
 
Repacking: Larger containers or material being distributed into smaller order quantities. 
 
Repeat deviation: A deviation that re-occurs after the identification of actions identified from a previous deviation. This would indicate that the root cause of the previous incident had not been correctly identified and/or that the actions determined had either not been taken in a timely manner, or had not effectively addressed the root cause.
 
Repeatability: The inherent variation in measurements due to the equipment. Causes include noise in electronics, variation in chemical solutions used in the measurement and other causes of random system fluctuations.
 

Reportable Result: The final value(s) that will be reported as representing the outcome of the analysis derived from the data. It is the value compared to the specifications.

Reprocessing: Taking the same material and repeating steps that are already part of the normal process.

Representative sample: A sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled. (FDA 21 CFR 210.3)
 
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. 
 
Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the established manufacturing process. Continuation of a process step after an in-process control test has shown that the step is incomplete, is considered to be part of the normal process, and is not reprocessing.
 
Reprocessing: Taking the same material and repeating steps that are already part of the normal process.
 
Reproducibility: The precision between two laboratories. It also represents precision of the method under the same operating conditions over a short period of time. The variation due to the effect of different operators using the same equipment. In this case excessive reproducibility signals a need for training and consistent procedures.
 
Resample: To take additional test samples from the same lot of material previously tested.
 

Reserve/ Reference samples: Term used for samples taken for retention.

Retest: To perform additional testing on the original sample (where possible) or new original sample according to an investigative plan, when no determinant error is found.
 
Retest Date: The date when a material should be re-examined to ensure that it is still suitable for use. Reworking: Subjecting an intermediate or API that does not conform to standards or specifications to one or more processing steps that are different from the established manufacturing process to obtain acceptable quality intermediate or API (e.g., recrystallizing with a different solvent). 
 
Re-test period: The period of time during which the drug substance is expected to remain within its specification and, therefore, can be used in the manufacture of a given drug product, provided that the drug substance has been stored under the defined conditions. After this period, a batch of drug substance destined for use in the manufacture of a drug product should be retested for compliance with the specification and then used immediately. A batch of drug substance can be retested multiple times and a different portion of the batch used after each retest, as long as it continues to comply with the specification. For most biotechnological/biological substances known to be labile, it is more appropriate to establish a shelf life than a retest period. The same may be true for certain antibiotics.
 
Return: Sending back to the manufacturer or distributor of a medicinal products which may or may not present a quality defect. 
 
Reworking:  Taking already manufactured material and performing steps that are not part of the normal process
 
Risk Assessment: An assessment of the risk associated with the non-conformity, defect, or other undesirable situation based on both safety and business components. The output is categorised into Major, Moderate, Minor or Incidental ratings. 
 
Robustness (ICH Q2): The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. 
 
Root CauseThe basic cause of a deviation, from which effective actions can be defined to prevent recurrence.
 
Run chart: Used to monitor manufacturing processes, a run chart specifies the target fill, lower and upper specification limits, and the actual volumes dispensed over time.

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S.

 
Sample: A generic term encompassing controls, blanks, unknowns, and processed samples, as described below:
 
i. Blank: 
A sample of a biological matrix to which no analytes have been added that is used to assess the specificity of the bioanalytical method. 
 
ii. Quality control sample (QC): 
A spiked sample used to monitor the performance of a bioanalytical method and to assess the integrity and validity of the results of the unknown samples analyzed in an individual batch. 
 
iii. Unknown: 
A biological sample that is the subject of the analysis. (Source: Guidance for Industry Bioanalytical Method Validation 2001- CDER)
 
Sampling booth: An area in the warehouse where starting and packaging materials are first sampled.
 
Sanitation: The reduction of microbiological contamination, usually achieved through cleaning as a preparation step, followed by the use of chemicals, biocides or disinfectants as sanitizing agents. The reduction in microbial load (the bio burden) by chemical means. The end result of sanitation does not guarantee the complete absence of micro-organisms.
 

Sanitization Schedules: Schedules established by the firm to sanitize the cleanroom facility surfaces, e.g., walls, ceilings, floors.  Schedules may vary depending on the use and condition of the room. The schedule is to be part of an approved procedure for housekeeping and cleaning of the aseptic area.

Seed lot system: A seed lot system is a system according to which successive batches of a product are derived from the same master seed lot at a given passage level. For routine production, a working seed lot is prepared from the master seed lot. The final product is derived from the working seed lot and has not undergone more passages from the master seed lot than the vaccine shown in clinical studies to be satisfactory with respect to safety and efficacy. The origin and the passage history of the master seed lot and the working seed lot are recorded. 
 
Seed material: A small amount of material used to start a chemical reaction, typically an approved lot of the material containing the desired crystal form which is added to start a crystallization process.
 
Seizure: An action by authorities, taken to remove a product from commerce because it is in violation of the law.
 
Selectivity: The ability of the bioanalytical method to measure and differentiate the analytes in the presence of components that may be expected to be present. These could include metabolites, impurities, degradants, or matrix components. 
 
Semi-permeable container: A container that allows the passage of solvent, usually water, while preventing solute loss. Examples of semipermeable containers include plastic bags and semirigid, low-density polyethylene (LDPE) pouches for large volume parenterals (LVPs), and LDPE ampoules, bottles, and vials.
 
Settling or settle plates: Usually petri dishes containing a microbial growth media, like agar, which are distributed throughout an area, media side up, to measure the viable content of the air over a specified period of time. This is a passive system that catches microorganisms as they fall onto plates.
 
Separate material: Inwards goods that have been separated on the basis of having different manufacturers’ batch or lot numbers and different delivery dates. Each separate material is allocated a Unique Identifying Number.
 
Shelf life: (Also referred to as expiration dating period) – The time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label.
 
Signed (signature): The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature
 
Solvent: An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API. 
 
Specification: Describes in detail the requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. (PIC/S, 4.1). Means a document which defines official tests, test methods and limits. Specifications usually relate to starting materials, components, bulk product and finished products but may also apply to critical steps of manufacture where failure to meet the acceptance criteria would result in defective product. Failure to meet specification results in Non-conforming product, formal QA investigations, rejection of material or product or reprocessing, and probably corrective action. 
 
Specification, release: The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug product at the time of its release.
 
Specification, shelf life: The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life.
 
Specificity (ICH Q2): Specificity is the ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). This definition has the following implications: 
 
i. Identification: 
To ensure the identity of an analyte. 
 
ii. Purity Tests: 
To ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte, i.e., related substances test, heavy metals, residual solvents content, etc. 
 
iii. Assay (content or potency): 
To provide an exact result which allows an accurate statement on the content or potency of the analyte in a sample.
 
Software Qualification: Provides evidence that the software has been designed, installed, and tested that ensures its performance meets its intended purpose, and that the system can be reinstalled in support of disaster recovery. 
 
(Software) Validation: Confirmation by examination and provision of objective evidence that (software) specifications conform to user needs and intended uses, and that the particular requirements implemented (through software) can be consistently fulfilled.
 
(Software) Verification: Verification provides objective evidence that design outputs of design development meet all specified requirements. (Software) verification looks for consistency, completeness (of software) and its supporting documentation. 
 
Specimen: Specimen means any material derived from a test system for examination or analysis 
 
Sponsor:
(1) A person who initiates and supports, by provision of financial or other resources, a nonclinical laboratory study; 
(2) A person who submits a nonclinical study to the Food and Drug Administration in support of an application for a research or marketing permit; or
(3) A testing facility, if it both initiates and actually conducts the study. 
 
Spores: A resistant body formed by certain micro-organisms.
 
Sporicide: Kills 100% of bacterial spores. 
 
Stability: The chemical stability of an analyte in a given matrix under specific conditions for given time intervals. (Source: Guidance for Industry Bioanalytical Method Validation 2001- CDER). The variation in accuracy with respect to time. This might be due to wear in the standard or a function of environmental conditions.
 
Stability-indicating assay: A validated quantitative analytical procedure that can detect the changes with time in the pertinent properties of the drug substance and drug product.
 
Standards: Measurement systems or artifacts, traceable to National or International Reference Standards, which are used to calibrate test equipment.
 
Standard name: A name assigned to a starting material that uniquely identifies it within the manufacturing establishment. It is used to cite the material in specifications, on identity/status tags, in analytical reports, in stores records and in batch documents. It is chosen to avoid the possibility of confusion between similar-looking or similar-sounding names.
 
Standard Names Register: A list containing the names used to label and identify starting materials during storage and manufacture. 
 
Standard curve: The relationship between the experimental response value and the analytical concentration (also called a calibration curve).
 

Standard Deviation (SD): A measure of the dispersion of a series of results around their average, expressed as the square root of the variance.

Starting material: Any substance used in the production of a medicinal products, but excluding packaging materials. 
 
Static /“at rest” testing: Testing performed with equipment installed but no personnel present to ensure that the facility environment continues to perform as designed and is compliant during normal operation
 
Statistic: A quantity associated with a sample taken from a population. (See parameter).
 
Statistical quality control: The specialized field of quality control using statistical methods such as the use of frequency distribution, measures of central tendency and dispersion, control charts, acceptance sampling, regression analysis etc.
 
Status label: Physical or electronic identification of a material indicating its status as “Quarantine”, “Hold”, “Released”, “Approved”, or “Rejected”.
 
Sterility: Sterility is the absence of living organisms. The conditions of the sterility tests are given in the European or other relevant Pharmacopoeia. The concept of the complete absence of living micro-organisms. The total elimination of any living organisms, usually by heat or chemical means, of any living organisms. 
 
Sterility test: A test performed on a sample of the product lot to determine if viable microorganisms are present.
 
Sterility assurance level (SAL): The SAL of a sterilizing process is the degree of assurance with which the process in question renders a population of items sterile. The SAL for a given process is expressed as the probability of a non-sterile item in that population. An SAL of 10-6 for example, denotes a probability of not more than one viable micro-organism in 1 × 106 sterilized items of the final product. The SAL of a process for a given product is established by appropriate validation studies.
 
Sterile: Free from all living organisms. 
 
Sterilization: (1) A process intended to produce sterile goods. (2) Reduction of the probability of the presence of viable micro-organisms to an acceptable extent. Sterilization is effected by moist or dry heat, by treatment with a gaseous sterilant such as ethylene oxide, by irradiation with ionizing radiation or, where such processes are inapplicable to solutions, by filtration. 
 
Sterile products: Sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product.
 

Sterility test: A test performed on a sample of the product lot to determine if viable microorganisms are present.

Sterilizing grade filter: A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent. 
 
Stock cultures: Pure microbial cultures that are kept for use in the lab. Sources of these cultures may be the American Type Tissue Collection or microorganisms isolated from the production environment.
 

Stop shipment: A drug shipment that is placed on hold pending investigation.

Storage condition tolerances: The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage conditions within the ranges defined in ICH Q1A(R2). The actual temperature and humidity (when controlled) should be monitored during stability storage. Short-term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed.
 
Stress testing (drug product): Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photostability testing (see ICH Q1B) and specific testing of certain products (for example metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products).
 
Stress testing (drug substance): Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing.
 
Study director: Study director means the individual responsible for the overall conduct of a nonclinical laboratory study. 
 
Study initiation date: Study initiation date means the date the protocol is signed by the study director. 
 
Study completion date: Study completion date means the date the final report is signed by the study director.
 

Supervisory control and data acquisition (SCADA): Application software used for process control and alarm management for the collection of data.

Supplier: An umbrella term that covers both Vendors and Contractors supplying API, intermediates, raw materials, packaging components, excipients, formulated products, packaged products and / or providing services, e.g. calibration, validation, laboratory testing etc. to the sponsoring firm.
 
System suitability testing: The evaluation of the components of an analytical system to show that the performance of a system meets the standards required by the method.
 
Supporting data: Data, other than those from formal stability studies, that support the analytical procedures, the proposed re-test period or shelf life and the label storage statements. Such data includes (1) stability data on early synthetic route batches of drug substance, small-scale batches of materials, investigational formulations not proposed for marketing, related formulations, and product presented in containers and closures other than those proposed for marketing; (2) information regarding test results on containers; and (3) other scientific rationales.
 
System suitability: Determination of instrument performance (e.g., sensitivity and chromatographic retention) by analysis of a reference standard prior to running the analytical batch.

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T. U. V. W. X.Y. Z.

 
Terminal sterilization: The application of a lethal agent to sealed, finished drug products for the purpose of achieving a predetermined sterility assurance level (SAL) of usually less than 10 -6 (i.e., a probability of a nonsterile unit of greater than one in a million).
 
Test article: Test article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act.
 
Test system: Test system means any animal, plant, microorganism, or subparts thereof to which the test or control article is administered or added for study. Test system also includes appropriate groups or components of the system not treated with the test or control articles.
 
Test Equipment:  Measurement systems used to calibrate critical instrumentation.
 
Testing facility: Testing facility means a person who actually conducts a nonclinical laboratory study, i.e., actually uses the test article in a test system. Testing facility includes any establishment required to register under section 510 of the act that conducts nonclinical laboratory studies and any consulting laboratory described in section 704 of the act that conducts such studies. Testing facility encompasses only those operational units that are being or have been used to conduct nonclinical laboratory studies.
 
Testing accelerated: Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. Data from these studies, in addition to long-term stability studies, can be used to assess longer term chemical effects at non-accelerated conditions, and to evaluate the effect of short-term excursions outside the label storage conditions, such as might occur during shipping. Results from accelerated testing studies are not always predictive of physical changes.
 
Theoretical yield: The quantity that would be produced at any appropriate phase of manufacture, processing, or packing of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production. (FDA 21 CFR 210.3)
 
Time-expire: Reach the use-by date.
 
Training plan: A plan established by site management for individual employees or employees within a single department stating what training (both regulatory and job skills training) is required for the employee to be considered competent in the job.
 
Traceability (General): The ability to trace the history, application or location of that which is under consideration (ISO 9000:2000).
 
Traceability (with respect to calibration): The ability to relate individual measurement results through a continuous sequence of measurement accuracy verifications, to nationally (or internationally) accepted measurement systems.
 
Trend: A determination that data is moving in a general direction based on the reoccurrence of events within a defined period of time.
 
Trend analysis: A periodic review and analysis of the Environmental Monitoring Program results that can be related to time, shift, facility, etc. for patterns that may suggest underlying or developing problems.
 
Type or Class A glassware: Glassware that conforms to applicable construction and accuracy requirements as certified by the American Society of Standards and Testing. This glassware is marked with the letter “A” on it.
 
ULPA filter: Ultra-low penetration air filter with minimum 0.3 ºm particle retaining efficiency of 99.999 percent.
 
Undetermined laboratory error: A situation where the laboratory investigation is inconclusive and the possibility remains that a laboratory error has eluded the investigation process.
 
Unidirectional flow: An airflow moving in a single direction, in a robust and uniform manner, and at sufficient speed to reproducibly sweep particles away from the critical processing or testing area.
 
Unique Identifying Number (UIN): A number or combination of numbers, symbols and letters which uniquely distinguishes a batch of product from all other batches of that product, or other products, at all stages of manufacture and permits a correspondence to be established between the batch and all tests carried out on it in the course of processing and quality control. The UIN for starting materials should be derived from a different system to that used for finished product batches. Alternately called the Goods Inward Number (GIN).
 
Upper limit of quantification (ULOQ): The highest amount of an analyte in a sample that can be quantitatively determined with precision and accuracy.
 
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).
 
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 attributes.
 
a. Prospective Validation:
Validation conducted prior to the distribution of either a new product or process. Documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol, are established.
 
b. Concurrent Process Validation:
Validation carried out during routine production of products intended for sale.
 
c. Retrospective Validation:
The conduct of validation studies performed after production has begun and designed to show that the processes and procedures etc. are capable of ensuring product consistently meets specification. Retrospective validation is often proceeded by retrospective review which involves the
assessment of accumulated manufacturing, testing and control data. Validation of a process for a product which has been marketed based upon accumulated manufacturing testing and control batch data.
 
d. Revalidation / Requalification:
Routine activities undertaken to confirm that critical systems, equipment and processes continue to operate in a validated state and in conformance with current GMPs.
 
e. Full validation
Establishment of all validation parameters to apply to sample analysis for the bioanalytical method for each analyte.
 
f. Partial validation:
Modification of validated bioanalytical methods that do not necessarily call for full revalidation.
 
g. Cross-validation:
Comparison validation parameters of two bioanalytical methods
 
h. Cleaning validation:
Sets out to prove that the documented cleaning procedure will consistently remove the previous product, cleaning agent, and reduce the microbial population to a safe and acceptable level.
 
i. Method Validation: 
The process by which it is established, by laboratory studies, that the performance characteristics of the analytical methods meet the requirements for the  intended application.
 
Validation Deficiency or Deviation Report: A form used to monitor and record circumstances which do not meet acceptance criteria or Code of Good Manufacturing Practice guidelines during the execution of validation.
 
Validation Plan: A document which defines the specific validation scope and associated activities of a project
 
Validation Protocol: A written plan stating how validation will be conducted. Including test parameters, product characteristics, production equipment and decision points on what constitutes acceptable test results.
 
Validation Protocol Supplement: A written document that presents supplementary information or planned changes to the original protocol..
 
Validation report: Document reporting the validation activities, the validation data and the conclusion drawn. 
 
Validation Form: A form developed to aid in the collection of the data specified in a Validation Protocol or Annual Review/Verification.
 
Validation Master File (Datapack): A file or datapack which contains all documents, reports and information concerning a validation activity. It is the permanent record of the objective evidence generated to demonstrate that a process, system or piece of equipment is in control and has been validated satisfactorily.
 
Validation documentation includes: 

– Overview and definition of the system (Requirements Specification)

– A Master Validation Plan or equivalent which provides schedules, standards, acceptance criteria, responsibilities for development and execution of protocols

– System design requirements (functional and technical specifications)

– Installation qualification protocols

– Operational and Performance qualifications that identify the critical parameters and functionalities to be qualified

– Worksheets that capture the test plan, test results and acceptance criteria
 
– Validation report that summarizes the protocol objectives, testing results and acceptance/rejection criteria from the test plan and protocol(s) and a statement that accepts or rejects the system
 
– Change control records.
 
Vegetative cells: A cell in the active stage of growing , as opposed to the resting or spore stage.
 
Vendor: Provider of API, raw material, excipients and packaging components to sponsoring firm. A vendor supplies articles of commerce (i.e. available for purchase by other companies).
 
Vent filter: A non-shedding porous material capable of removing viable and non-viable particles from gases passing in and out of a closed vessel.
 
Viruses: Viruses are basically packages of genetic material wrapped in a protein coat. They are parasites and incapable of independent growth and replication outside a host cell.
 
Violative product: A drug product produced or manufactured in violation of the Federal Food, Drug, and Cosmetic Act.
 
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.
 
Warning Letter: A letter sent by the Food and Drug Administration (FDA) to management of a company indicating that GMP violations were found in a recent inspection and what the violations were. The expectation is that the company will respond within a designated time period with an acceptable corrective action plan.
 
Water for Injection: Water produced by a suitable method (e.g., distillation) from potable water, usually with an intermediate purification step(s), to meet specifications as defined by a compendial monograph.
 
Worst case: A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure.
 
Conditions within normal parameters most likely to give failure. For processing purposes, “worst case” means those values of normal operating parameters most likely to cause process failure. For sampling locations, “worst case” means those equipment locations most likely to have higher levels of residues after cleaning. For sampling recovery, “worst case” means those procedures, within normal sampling parameters, most likely to give poorer percentage recovery.
 
Yeast: A type of fungus that is uni-cellular and lacks typical mycelia.
 
Yield: A way of looking at material balance, focusing on acceptable product outputs. As opposed to reconciliations (used in packaging and labelling), yield calculations are usually used during production processes.
 
Yield, actual: Actual yield is the quantity of acceptable material or product that is output at an intermediate or final stage of manufacture.
 
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.
 
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.

240 SOPs, 197 GMP Manuals, 64 Templates, 30 Training modules, 167 Forms. Additional documents included each month. All written and updated by GMP experts. Checkout sample previews. Access to exclusive content for an affordable fee.