Terms and their Definitions used in Pharmaceutical Industry

A

Abbreviated New Drug Application (ANDA) - An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public.

Accelerated Stability Studies/ Accelerated Testing – These studies are done to predict the shelf life of the product by increasing the rate of decomposition or by mostly increasing the temperature of reaction conditions. These testing provide evidence how quality of the product varies with time and recommend storage conditions, container closure system suitability.

Acceptance Criteria: The specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan that are necessary for making a decision to accept or reject a lot or batch of raw material, intermediate, packaging material, or active pharmaceutical ingredient. This term can also be applied to validation.

Accountability - Quality of subordinate workers being responsible for their own work and answerable to a supervisor

Accreditation - Procedure by which an accreditation body gives formal recognition that a laboratory or person is competent to carry out specific tasks

Accreditation body - Independent science-based organization which has the authority to grant accreditation

Accuracy - The degree of agreement between a measured value and the accepted reference value.

Action Limits - The range limits which include 99.7 % of the results (±3 standard deviations). Any results laying outside these limits requires an immediate corrective action.

Action Level- An established microbial or airborne particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation.

Active Pharmaceutical Ingredient (API) - Any substance or combination of substances used in a finished pharmaceutical product (FPP), intended to furnish pharmacological activity or to otherwise have direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to have direct effect in restoring, correcting or modifying physiological functions in human being .

Active Substance Master File (ASMF) / European Drug Master File (EDMF) - This allows valuable confidential intellectual property of the manufacturer of the active substance (ASM) to be protected and allows the Marketing Authorisation (MA) or Applicant holder to take full responsibility for the medicinal product and the quality and quality control of the active substance.

Active Systems - Actively powered systems using electricity or other fuel source to maintain a temperature-controlled environment inside an insulated enclosure under thermostatic regulation

Administrative Review - Procedure used to check for consistency with laboratory policy and for editorial correctness. This review may be performed by the author of the report or other personnel

Adverse Drug Reactions (ADRs)  - A response to a medicinal product that is noxious or potentially harmful and unintended and which occurs at doses normally used in human for prophylaxis, diagnosis or therapy of a disease or for the modification of physiological function in which individual factors may play an important role.

Adverse Event or Experience - Any unfavorable medical occurrence that in coincidence may present during treatment with a pharmaceutical product, but which does not necessarily have a causal relationship with the treatment

Adverse Drug Reaction (ADR) Case Report - A case report in ADR monitoring programme is a notification relating to a patient with an adverse effect or laboratory test abnormality suspected to be induced by a medicinal product

Aerobic Organisms – These are the organisms that need oxygen to make energy through a process called cellular respiration where they take glucose (sugar) and oxygen to make energy (adenosine triphosphate, or ATP) and carbon dioxide.

Aerosols – It refers to the fine mist of spray which results from most pressurized systems. They are packaged under pressure and contain therapeutically active ingredients which released on activation of valve system.

Agglomerates -They are particulate materials consisting of large particles formed by the joining or binding together of primary particles whose original identity can still be visible in the final agglomerate form and this process is called agglomeration.

Aggregation- It is the massing or clumping of materials together.

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

Air Filter – It is an unit installed in air handling system which is designed to remove particulates from the air passing through it.

Air Flow – Air flow is distribution of air passing through a filter element per unit of time. It is expressed in ft³/ min or CFM (m³/h or m³/ s).

Airborne Particles – solid or liquid matter which are suspended in air and the size of particles may vary and are expressed in µm

Airborne Particulate Count/ Total Particulate Count – Particles detected are 0.5µm and larger. When a number of particles are specified it is the maximum allowable number of particles per cubic meter of air or per cubic foot of air

Airborne Viable particulate Count/ Total Airborne Aerobic Microbial Count – When a number of microorganisms are specified it is the maximum number of colony forming units (cfu) per cubic meter of air or per cubic foot of air that is associated with a cleanliness class of controlled environment based in the airborne particulate count.

Air Changes – The frequency per unit of time (minutes, hours) that the air within a controlled environment is replaced. The air can be recirculated partially or totally replaced

Air Changes Per Hour (ACPH) - The volume of air supplied to a room, in m3/hr, divided by the room volume, in m3

Air Handling Unit (AHU) - Air handling unit which serves to condition the air and provide the required air movement within a facility

Air Sampler – Devices or equipment used to sample a measured amount of air within a controlled environment is replaced. The air can be recirculated partially or totally replaced

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

Aliquot - Portion of a liquid sample or solution

Amorphous – Substances without definite shape or visible differentiation in structure or not crystallized.

Analgesics - They are the medicines that relieve pain.

Angle of Repose – It is the maximum angle from horizontal at which a given material will rest on a given surface without sliding or rolling.

Analysis of Variance (ANOVA) - Statistical technique which can be used to separate and estimate the different causes of variation

Analytical Procedure - It is developed to test a defined characteristic of the drug substance or 99 drug product against established acceptance criteria for that characteristic.

Anemometer - Anemometer measure the speed (velocity) of moving air.

Antacids – They are the medicines that control the acid levels in stomach.

Antiemetics –They are the medicines taken to prevent or treat nausea and vomiting

Antiflatulents – They are the medicines used for the alleviation or prevention of excessive intestinal gas, i.e., flatulence.

Antineoplastic Agents – They are used to prevent, inhibit or halt the development of a neoplasm (a tumor).

Antipyretic Agents – These are the agents that reduces fever

Anaerobic Organism - An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It may react negatively or even die if oxygen is present.

Analyte - It is a substance or material determined by a chemical analysis.

Analytical batch or run: Complete set of analytical samples with an appropriate number of standards and quality control samples 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 System (Measurement System) - Complete set of measuring instruments and other equipment assembled to carry out a specified measurement task. In the context of analyzing controlled drugs in seized materials or biological specimens, the analytical system consists of the laboratory balance(s), pH meter, chromatograph, thin layer chromatography equipment, etc. which are used by the analyst to carry out the analysis.

Annual Product Quality Review (APQR) - It is an evaluation which is prepared according to the cGMP requirements of different regulatory authorities.

Archive - Collection of documents and records purposefully stored for a defined period of time

Arithmetic Mean or Average - Sum of the individual values in a set divided by the number of values

Arrestance – It is the removal of standard test dust

Assay - Quantitative measurement of an analyte

As-built - Condition where the installation is complete with all services connected and functioning but with no production equipment, materials, or personnel present.

Aseptic Filling - The filling of cans or other containers with food that has already been sterilized, the process thus having to be carried out under aseptic conditions

Aseptic Manufacturing Area- The classified part of a facility that includes the aseptic processing room and ancillary cleanrooms. For purposes of this document, this term is synonymous with “aseptic processing facility” as used in the segregated segment context.

Aseptic Processing Facility- A building, or segregated segment of it, containing cleanrooms in which air supply, materials, and equipment are regulated to control microbial and particle contamination

Aseptic Processing Room- A room in which one or more aseptic activities or processes is performed

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

At-rest - Condition where the installation is complete with equipment installed and operating in a manner agreed upon by the customer and supplier, but with no personnel present.

Audit - Independent review conducted to compare the various aspects of the laboratory’s performance with a standard for that performance. Also defined as a systematic, independent and documented process for obtaining audit evidence and evaluating it objectively to determine the extent to which audit criteria are fulfilled.

Auditors - Personnel who carry out an audit. They can be internal, involving suitably trained personnel from within the laboratory’s own organization, or external, for example from an accreditation body or other independent organizations

Audit trail - Detailed records kept of actions carried out by personnel such that subsequent examination of the records by an auditor would allow a sequence of actions to be recreated or understood. Examples of an audit trail include (a) records of which member of staff did what work, when it was done, procedures used, instruments used etc; (b) records of changes made in documents, laboratory procedures, results and reports, who made the changes, when they were made, the reasons why they were made, and who authorized the changes. An electronic audit trail is a recording system built in to a computer-based system which keeps a record of all changes of the types mentioned

Authorization - Process by which personnel or procedures are approved for the work of the laboratory by suitably qualified staff

Authorized Person - The person recognized by the national regulatory authority as having the responsibility for ensuring that each batch of finished product has been manufactured, tested and approved for release in compliance with the laws and regulations in force in that country.

Available Sample - Whatever total quantity of sample materials is available

B

Barcode - A graphical representation of a product's identifying information formed by a two-dimensional pattern of black and white shapes. Barcodes are able to be read by optical devices, such as a barcode reader or scanner

Barrier System - Physical barriers installed within an aseptic processing room to provide partial separation between aseptically gowned personnel and critical areas subject to considerable contamination risk. Personnel access to the critical zone is largely unrestricted. It is subject to a high level disinfection.

Batch / Lot - A defined quantity of starting material, or product processed in a single process or series of processes so that it is expected to be homogeneous.

Batch Number/Lot Number - A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis, etc

Batch Records - All documents associated with the manufacture of a batch of bulk product or finished product. They provide a history of each batch of product and of all circumstances pertinent to the quality of the final product.

Bias - The difference between the expectation of the test results and an accepted reference value. Bias is the total systematic error as contrasted to random error. There may be one or more systematic error components contributing to the bias. A larger systematic difference from the accepted reference value is reflected by a larger bias value.

Biological Matrix - A discrete material of biological origin that can be sampled and processed in a reproducible manner

Binders – They are used in the formulation of solid oral dosage forms to hold the active pharmaceutical ingredient and inactive ingredients together in a cohesive mix. Binder products are usually differentiated based on the manufacturing process to be used

Binding - Binding in the die refers when the tablets adhere, seize or tear in the die. A film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are cracked and it may crumble apart.

Bioequivalence – It is defined as the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

Bioavailability - The percent of dose entering the systemic circulation after administration of a given dosage form. More explicitly, the ratio of the amount of drug “absorbed” from a test formulation to the amount “absorbed” after administration of a standard formulation. Frequently, the “standard formulation” used in assessing bioavailability is the aqueous solution of the drug, given intravenously.

Bioburden - Bioburden is defined as the number of bacteria living on a surface that has not been sterilized.

Biological indicator – It is defined as characterized preparation of a specific microorganism which provides a defined and stable resistance to a specific sterilization process. It is used to assist in the performance qualification of the sterilization equipment and in the development and establishment of a validated sterilization process for a particular article.

Biopharmaceutics - The science and study of the ways in which the pharmaceutical formulation of administered agents can influence their pharmacodynamic and pharmacokinetic behavior. Differences in pharmaceutical properties can cause substantial differences in the biologic properties – and therapeutic usefulness – of preparations which are identical with respect to their content of active ingredient. Pharmaceutical properties known to influence the therapeutic efficacy of drugs like appearance and taste of the dosage form, solubility of the drug form used in the preparation, the nature of “fillers”, binders, or menstrua in the dosage form, particle size etc.

Biosimilar - A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products

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

Blending - Blending is a process of combining materials, but blending is a relatively gentle process compared to mixing. In terms of the phase of material, blending is the process of solid-solid mixing or mixing of bulk solids with small quantity of liquid. The terminology mixing is more closely associated with liquid-liquid, gas-liquid, and viscous materials

Blind specimen or sample: Specimen or sample that is analysed by an operator who is unaware at the time of the analysis that the sample is for control purposes

Blister pack - Blister pack is a term for several types of pre-formed plastic packaging used for small consumer goods, foods, and for pharmaceuticals. The primary component of a blister pack is a cavity or pocket made from a formable web, usually a thermoformed plastic.

Blow Fill Seal (BFS) - Blow-fill-seal processes create plastic vials, fill them with aseptic drugs, and seal them, all with minimal human interaction. The extrusion process prevents microbes and endotoxins from contaminating vial contents. Containers produced by the blow-fill-seal process can incorporate molded-in features for safer, more-ergonomic drug administration.

Borescope - A borescope is an optical device consisting of a rigid or flexible tube with an eyepiece on one end, an objective lens on the other linked together by a relay optical system in between. The optical system in some instances is surrounded by optical fibers used for illumination of the remote object. Borescopes are mostly used in nondestructive testing techniques for recognizing defects or imperfections

Body - Hard-shelled capsules made using gelatin and contain dry, powdered ingredients or miniature pellets made by extrusion or spheronisation. These are made in two halves: a lower-diameter "body" that is filled and then sealed using a higher-diameter "cap".

Bovine - Originated from cows and cattle

Bovine Spongiform Encephalopathy (BSE) / Mad Cow Disease - It is a progressive neurological disorder of cattle that results from infection by an unusual transmissible agent called a prion.

Bowie Dick test - The verify Bowie Dick Test Pack consists of a series of air removal and steam penetration barriers. A chemical indicator is located in the center of each pack. The test pack is placed directly into an otherwise empty steam sterilizer chamber and does not require a retaining device. During processing, steam must displace the air through the barrier material within the pack. A uniform change from yellow to blue/purple on the indicator sheet indicates that all the air was removed and replaced by steam.

Bracketing - The design of a stability schedule such that only samples on the extremes of certain design factors like strength and package size are tested at all time points as in a full design. The design assumes that the stability of any intermediate level is represented by the stability of the extremes tested.

Bronchodilator - Bronchodilators are medications commonly used by people with asthma. They relax the muscles that surround the airways and allow the airways (the tubes that carry air into and out of the lungs) to open up.

Brittleness - Tendency of a material to fracture or fail upon the application of a relatively small amount of force, impact, or shock.

Bubble point test - A bubble point test is a test designed to determine the pressure at which a continuous stream of bubbles is initially seen downstream of a wetted filter under gas pressure. To perform a Bubble Point Test, gas is applied to one side of a wetted.

Bulk density - The bulk density of a powder is the ratio of the mass of an untapped powder sample and its volume including the contribution of the interparticulate void volume. Hence, the bulk density depends on both the density of powder particles and the spatial arrangement of particles in the powder bed.

Bulk product - Any product that has completed all processing stages up to, but not including, final packaging

C

Calibration - The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding 41 known values of a reference standard. Limits for acceptance of the results of measuring should be established.

Calibration Curve - Relationship between the signal response of the instrument and various concentrations of analyte in a suitable solvent or matrix

Calibration Interval - Frequency of specific performance tests that are made on each instrument or item of equipment as part of the laboratory’s preventive maintenance programme.

Calibration Laboratories - Laboratories that perform calibrations.

Calibration Method - Defined technical procedure for performing a calibration.

Calibration Record(s) - Record(s) usually maintained in instrument or equipment logbooks that contain details of calibrations carried out, dates on which they were performed and the operator(s) involved. Calibrations may be carried out by internal personnel or external organizations. The latter may provide the laboratory with a calibration certificate.

Calibration Standard - 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 quality control and unknown samples are determined.

Calibrator - Pure analyte in a suitable solvent or matrix used to prepare the calibration curve. Calibrators are similar in composition to controls but must be prepared separately from them, since controls are used to check on the accuracy of the calibration curve

Candidate Method - Analytical method which has been selected and developed for a particular analytical problem and which must be validated to show that it is fit for the intended analytical purpose before being used.

Case Records - All notes, reports, chain of custody records, charts, analytical data, and any correspondence generated in the laboratory pertaining to a particular case

Case Review - Scrutiny of documents pertaining to a case, usually by a senior member of staff, to ensure that the case has been processed according to the laboratory’s specified procedure. The review would include a check on submission forms, chain of custody records, analytical results and interpretations and of the final report

Cap - Hard-shelled capsules made using gelatin and contain dry, powdered ingredients or miniature pellets made by extrusion or spheronisation. These are made in two halves: a lower-diameter "body" that is filled and then sealed using a higher-diameter "cap".

Caplet - A smooth, coated, oval-shaped medicine tablet intended to be tamper-resistant.

Capping – It is used when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling.

Capability of a Process – It is the ability of a process to produce a product that will fulfill the requirements of that product. The concept of process capability can also be defined in statistical terms.

Certification - Procedure by which a certifying body gives formal recognition that an organization, person, process, service or product complies with given specifications

Certification of Suitability (CEP) - The CEP is facilitating and simplifying exchanges between the partners to ensure that the quality of substances is guaranteed and that these substances comply with the European Pharmacopoeia and therefore the requirements of EU directives for medicines.

Certified Reference Material (CRM) - Reference material one or more of whose property values are certified by a technical procedure, accompanied by or traceable to a certificate or other documentation which is issued by a certifying body.

Certifying Body - Independent science-based organization which has the competence to grant certifications. The certifying body may or may not be accredited

Chain of Custody/Chain of Evidence - Procedures and documents that account for the integrity of a specimen or sample by tracking its handling and storage from its point of collection to its final disposition.

Check Sample - Test sample used to ensure that the performance characteristics of an instrument are being maintained.

Chirality - Property of a molecule not to be superimposable on its mirror image. Owing to asymmetry in their structures these molecules can exist as different isomers and will have special optical and biological properties

Changes Being Effected - A moderate change may have the potential to cause adverse effects in terms of identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product. FDA may identify certain moderate changes for which distribution can occur when FDA receives the supplement. This type of supplement is called, and should be clearly labeled, a Supplement - Changes Being Effected.

Changes Being Effected in 30 Days - One type of moderate change requires the submission of a supplement to FDA at least 30 days before the distribution of the drug product made using the change. This type of supplement is called, and should be clearly labeled, a Supplement - Changes Being Effected in 30 Days.

Change Control - Change control is an important element in any Quality Assurance system. Written procedures should be in place to describe the actions to be taken if a change is proposed to a product component, process equipment, process environment (or site), method of production or testing or any other change that may affect product quality or support system operation.

Change Management - The Change Management process establishes an orderly and effective procedure for tracking the submission, coordination, review, evaluation, categorization, and approval for release of all changes to the project’s baselines.

Changeover - In manufacturing, changeover is the process of converting a line or machine from running one product to another. Changeover times can last from a few minutes to as much as several weeks.

Chemistry, Manufacturing, and Control (CMC) - Drug development must establish the physicochemical properties of the NCE: its chemical makeup, stability, and solubility. Manufacturers must optimize the process they use to make the chemical so they can scale up from a medicinal chemist producing milligrams, to manufacturing on the kilogram and ton scale. They further examine the product for suitability to package as capsules, tablets, aerosol, intramuscular injectable, subcutaneous injectable, or intravenous formulations. Together, these processes are known in preclinical development as chemistry, manufacturing, and control (CMC).

Child-Resistant (C-R) Packaging / Special packaging - It is used to reduce the risk of poisoning in children via the ingestion of potentially hazardous items including certain prescription and over-the-counter (OTC) medications, pesticides, and household chemicals.

Chipping/Erosion - The edges of the tablets are worn away, or chipped, as the coating is being applied.

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.

Cleanroom- A room designed, maintained, and controlled to prevent particle and microbiological contamination of drug products. Such a room is assigned and reproducibly meets an appropriate air cleanliness classification.

Clean Zone – A defined space in which the concentration of airborne particles and microorganisms are controlled to meet specific cleanliness class levels

Cleaning In Place (CIP) – It removes to removal of precipitates deposits or other matter adhering to the surface not to the initial cleaning after fabrication

Cleaning Validation - Documented evidence to establish that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration factors such as batch size, dosing, toxicology and equipment size

Clean Hold Times - The time elapsed from the end of the cleaning process until the beginning of the use of the cleaned equipment for manufacture of the next product

Client - Person, group or organization which submits samples to a laboratory for analysis. Clients may be internal, for example, from another department within the laboratory’s own organization, or external, for example, another organization

Climatic Zones - The four zones into which the world is divided based on the prevailing annual climatic conditions

Closed System - A system where the product or material is not exposed to the manufacturing environment.

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.

Contamination Recovery Rate - The contamination recovery rate is the rate at which environmental samples are found to contain any level of contamination.

Common Carrier - A seller of distribution services

Combined Sample - Sample resulting from combining all or parts of two or more samples of the material

Co-chromatography - Procedure for the identification of an unknown substance by chromatographic comparison with a known substance in which, prior to the chromatographic step

Coefficient of Variation or Relative Standard Deviation - Measure used to compare the dispersion or variation in groups of measurements. It is the ratio of the standard deviation to the mean, multiplied by 100 to convert it to a percentage of the average.

Collaborative Studies - Organization, performance and evaluation of tests on the same or similar items or materials by two or more different laboratories in accordance with predetermined conditions. The main purpose is validation of analytical methods or establishment of reference methods.

Competence - Ability to carry out a task correctly. The term takes on additional meaning under ISO/IEC 17025, as laboratory personnel are required to establish and maintain competence in all procedures which are accredited to the standard.

Competency test - Evaluation of a person’s ability to perform work in any functional area prior to the performance of independent casework

Compliance - Demonstrable proof that a laboratory has set up documented procedures to implement all of the requirements of a recognized standard (such as ISO/IEC 17025). If these procedures are verified by an external agency which can certify that they are in place, are used and are effective, then the laboratory is eligible for accreditation.

Computer Validation - Documented evidence which provides a high degree of assurance that a computerized system analyses, controls and records data correctly and that data processing complies with predetermined specifications.

Concentration - Amount of a substance, expressed in mass or molar units, in a unit volume of fluid or mass of solid.

Confidence level or Confidence coefficient - Measure of probability associated with a confidence interval expressing the probability of the truth of a statement that the interval will include the parameter value.

Confidence Limits - Extreme values or end values in a confidence interval.

Confirmatory Test - Second test by an alternate chemical method for unambiguous identification of a drug or metabolite

Contract Review - Procedures to ensure that the requirements of its clients are adequately defined, documented and understood and that it has the capability of meeting these requirements before agreeing (making a contract) to do the work.

Contractor: Organization that provides a certain service under contractual conditions. It should be ensured that the contractor provides services in line with specified criteria of competence.

Control chart: Graphical plot of test results with respect to time or sequence of measurements, with limits drawn within which results are expected to lie when the analytical scheme is in a state of statistical control

Consignment / Delivery - The quantity of a pharmaceutical(s), made by one manufacturer and supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include material belonging to more than one batch.

Containment - A process or device to contain product, dust or contaminants in one zone, preventing it from escaping to another zone

Contamination - The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or on to a starting material or intermediate during production, sampling, packaging or repackaging, storage or transport.

Confidence Intervals - The confidence interval of a measurement or set of measurements is the range of values that the measurement may take with a stated level of uncertainty.

Controlled or Hazardous Time- and Temperature-Sensitive Pharmaceutical Products - Time- and temperature-sensitive pharmaceutical products (TTSPPs) with high illicit value: poisons, narcotics, psychotropic products, inflammable or explosive substances and radioactive materials.

Controlled Environments – Any area in an aseptic process system for which airborne particulate and microorganism levels are controlled to specific levels, appropriate to the activities conducted within that environment

Controls - Specimens used to determine the validity of the calibration, that is, the linearity and stability of a quantitative test or determination over time. Controls are either prepared from the reference material (separately from the calibrators, that is, weighed or measured separately), purchased, or obtained from a pool of previously analysed specimens. Where possible, controls should be matrix-matched to specimens and calibrators

Positive control: Control that contains the analyte at a concentration above a specified limit.

Negative control: Control that contains the analyte at a concentration below a specified limit. Usually a drug-free specimen (blank) is used as a negative control.

Control Strategy - A planned set of controls, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to API and finished pharmaceutical product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications and the associated methods and frequency of monitoring and control.

Continued Process Verification - Documented scientific evidence that the process remains in a state of control during commercial manufacture

Commercial Manufacturing Process – It is the manufacturing process resulting in commercial product (i.e., drug that is marketed, distributed, and sold or intended to be sold). For the purposes of this guidance, the term commercial manufacturing process does not include clinical trial or treatment IND material.

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

Commissioning of a Controlled Environment – Certification by engineering and quality control that the environment has been built according to the specifications of the desired cleanliness class and that, under conditions likely to be encountered under normal operating conditions or worst case conditions, it is capable of delivering an aseptic process. Commissioning includes media-fill runs and results of the environmental monitoring program.

Concurrent Validation - Validation carried out during routine production of products intended for sale

Concurrent Release - Releasing for distribution a lot of finished product, manufactured following a qualification protocol, that meets the lot release criteria established in the protocol, but before the entire study protocol has been executed.

Correction for Recovery - Recovery of analytes in a method is frequently less than 100%. If there is no internal standard (which automatically compensates for incomplete recovery) then the results of analysis must be multiplied by a correction factor to obtain the values which would have been produced if the recovery had been 100%. This implies that the recovery of the method is known, which will be true if the method has been validated, as recovery is one of the performance characteristics which is measured

Corrective and Preventive Action (CAPA) - It is a deviation management program that focuses on the systematic investigation of discrepancies, adverse events, or failures

Correlation Coefficient - Number showing the degree to which two variables are related. Correlation coefficients range from 0 (no correlation) to –1 or +1 (perfect correlation)

Crime/Forensic Laboratory - Laboratory which employs one or more full-time scientists whose principal function is the examination of physical evidence for use in legal proceedings and who provide testimony with respect to such physical evidence to the courts.

Critical Parameter or Component - A processing parameter (such as temperature or humidity) that affects the quality of a product, or a component may have a direct impact on the quality of the product.

Critical Zone - Typically the entire area where product and the containers and closures are exposed in aseptic processing

Cross Reactivity - Response (of method) to analogues, metabolites, or other non-target components that may be present in the matrix.

Cross-Reacting Substances: In immunoassays, a substance that reacts with antiserum produced for the target analyte

Critical Area - An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas.

Critical Operation - An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical product

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

Cross-Contamination - Contamination of a starting material, intermediate product or finished product with another starting material or product during production.

Critical Operation - An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical product

Cross-Validation - A comparison of validation parameters when two or more bioanalytical methods are used to generate data within the same study or across different studies. An example of cross-validation would be a situation where an original validated bioanalytical method serves as the reference and the revised bioanalytical method is the comparator.

Critical Process Parameter - A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored and/or controlled to ensure the process produces the desired quality.

Critical Quality Attribute - A physical, chemical, biological or microbiological property or characteristic of materials or products that should be within an appropriate limit, range or distribution to ensure the desired product quality

Critical Variable Study - A study that serves to measure variables (parameters) critical to the satisfactory operation of a piece of equipment or plant and to assure their operation within monitored and controlled limits, Examples of variables would be pressure, temperature, flow rates, time etc

Cut-off Concentration - Concentration of a drug in a specimen used to determine whether the specimen is considered positive or negative. In some circumstances it is recommended that the cut-off concentration should be set equal to the limit of detection

D

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

Deficiency – Inadequacy or lacking in some necessary quality or element. Deficiencies include missing data, incomplete data, or incomplete reports

Degrees of Freedom - Number of independent comparisons which can be made between the members of a sample

Design Condition - Design condition relates to the specified range or accuracy of a controlled variable used by the designer as a basis to determine the performance requirements of an engineered system

Design Qualification (DQ) - Documented evidence that the premises, supporting systems, utilities, equipment and processes have been designed in accordance with the requirements of GMP.

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

Detection Frequency: The frequency with which contamination is observed in an environment. Typically expressed as a percentage of samples in which contamination is observed per unit of time

Deviation - Departure from what is considered normal

Direct Impact System - A system that is expected to have a direct impact on product quality. These systems are designed and commissioned in line with Good Engineering Practice (GEP) and, in addition, are subject to Qualification Practices

Discrepancy - Any reported results which differ from the consensus results. Discrepancies may be classified as administrative, systematic, analytical or interpretive

Discrimination - Ability to recognize and understand the differences between two things. Also, the ability of a measuring instrument to respond to small changes in the value of the stimulus

Disinfection- Process by which surface bioburden is reduced to a safe level or eliminated. Some disinfection agents are effective only against vegetative microbes, while others possess additional capability to effectively kill bacterial and fungal spores.

Distribution - A ranking, from lowest to highest, of the values of a variable and the resulting pattern of measures or scores, as these are often plotted on a graph. A frequency distribution, for example, gives the possible values of a parameter versus the number of times each value occurred in the sample or population. In many instances it refers to the spread of the individual values of a sample or population around the mean.

Distribution Function - The distribution function F(x) of a variate x is the total frequency of members with variate values less than or equal to x. As a general rule, the total frequency is taken to be unity, in which case the distribution function is the proportion of members bearing values less than or equal to x

Document Control - Mechanism by which quality management system documents are created and amended, reviewed, approved, distributed and archived to ensure that all staff use the latest authorized versions.

Double Blind Procedure - Means of reducing bias in an experiment, for example in the clinical context, by ensuring that both those who administer a treatment and those who receive it do not know (are blind to) which subjects are in the control and experimental group, that is, who is and is not receiving the treatment.

Drug /Medicinal product - Any substance or mixture of substances manufactured, sold or presented for use in the diagnosis, treatment, mitigation or prevention of a disease, disorder, abnormal physical or mental state, or the symptoms thereof, in human or animal or restoring, correcting or beneficial modification of organic or mental functions in human or animal.

Duplicate Samples or Specimens - Two aliquots of a sample or specimen analysed at the same time.

Dynamic Range - Range over which a relationship exists between analyte concentration and assay response

Dynamic- Conditions relating to clean area classification under conditions of normal production.

D value- The time (in minutes) of exposure at a given temperature that causes a one-log or 90 percent reduction in the population of a specific microorganism.

E

Efficiency – It is the percentage of the removal of the number of defined particles by the air filter in relation to the upstream concentration

End Determination or End-Step Determination - Final step in a sequence of stages comprising an analytical method, usually involving the application of a technique to an extract or other sample preparation to produce data on the composition of the sample

Energy efficiency – It is the ability of the air filter to reduce electricity consumption as  a function of its operating resistance and operating conditions

Environmental Isolates – Microorganisms that have been isolated from the environmental monitoring program.

Environmental Monitoring Program – Documented program, implemented through standard operating procedures that describes in detail the procedure and methods used for monitoring particulates as well as microorganisms in controlled environments. The program includes sampling sites, frequency of sampling, and investigative and corrective actions that should be followed if alert or action levels are exceeded. The methodology used for trend analysis is also described.

Endotoxin- A pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall. Endotoxin can lead to reactions in patients receiving injections ranging from fever to death.

Equipment - In general, the apparatus required for any operation.

Equipment Layout – It is a graphical representation of an aseptic processing system that denotes the relationship between and among equipment and personnel. This layout is used in the risk assessment analysis to determine sampling site

Error - Something done which is considered to be incorrect or wrong

Evaluation - Systematic examination of the extent to which a product, process or service fulfils specified requirements

Examination - Set of operations having the object of determining the value or characteristics of a property. In some disciplines (e.g. microbiology) an examination is the total activity of a number of tests, observations or measurements.

Exfiltration - Exfiltration is the egress of air from a controlled area to an external zone

Expiry Date - The date given on the individual container (usually on the label) of a drug product up to and including which the product is expected to remain within specifications, when stored under specified conditions. It is established by adding the shelf-life period to the date of manufacture.

Experimental Starting Date - The date on which the first study specific data are collected

Experimental Completion Date - The last date on which data are collected from the study.

Expert Witness - Appropriately qualified/experienced person, for example, a forensic scientist, familiar with the testing, evaluation and interpretation of test results. An expert witness is recognized by the court to provide opinion evidence

External Standard - Standard prepared directly from a reference substance, for example as a stock solution or serial dilutions of the stock solution. It is not prepared in the same type of matrix as the specimens or samples for analysis and therefore there is no requirement for an extraction step prior to analysis.

F

Facility - The built environment within which the clean area installation and associated controlled environments operate together with their supporting infrastructure.

Failure Mode - Different ways that a process or subprocess can fail to provide the anticipated result

Failure mode, Effects and Criticality Analysis (FMECA) - A systematic method of identifying and preventing product and process problems

False Negative - Test result which states that no drug or metabolite is present when, in fact, such a drug or metabolite is present in an amount greater than a threshold or a designated cut-off concentration.

False Positive - Test result which states that a drug or metabolite is present when, in fact, such a drug or metabolite is not present or is present in an amount less than a threshold or a designated cut-off concentration.

False Positive or False Negative Rate – It is a measure of reliability of a method which indicates the percentage of false negative and false positive results. The numbers of true positives/negatives are obtained using a reference method and compared with the numbers of positives/negatives obtained from the test method using the following equations:

False positive rate (%) = false positives x 100/true negatives

False negative rate (%) = false negatives x 100/total known positives

In the absence of a reference method, negative and positive fortified samples must be analysed.

Federal Standard 209E – Airborne particulate Cleanliness Classes in Clean Rooms and Clean Zones” is a standard approved by the commissioner, federal Supply Services, General Service Administration, for the use of “All Federal Agencies”. The standard establishes classes of air cleanliness based on specified concentration of airborne particulates. These classes of air cleanliness have been developed, in general, for the electronic industry “super clean” controlled environments. In the pharmaceutical industry, the federal Standard 209E is used to specify the construction of controlled environment. Class 100, Class 10,000 and Class 100,000 are generally represented in an aseptic processing system. If the classification system is applied on the basis of particles equal to or greater than 0.5µm, these classes are now represented in the SI system by class M3.5, M5.5 and M6.5.

Finished Pharmaceutical Product (FPP) - A finished dosage form of a pharmaceutical product that has undergone all stages of manufacture, including packaging in its final container and labelling

Finished Product - A finished dosage form that has undergone all stages of manufacture, including packaging in its final container and labelling

Filter Class – Indication of the air filtration performance measured according to test procedures

Filter Integrity – The degree to which the air filter demonstrates a consistent performance according to specification without leakage

Filter Qualification – It is the degree to which the air filter demonstrates a consistent performance according to specification without leakage

Final Sample - Sample ready for the application of the test procedure

Fitness for Purpose – It is the degree to which data produced by a measurement process enables a user to make technically and administratively correct decisions for a stated purpose.

Fit for Purpose - A laboratory method that is fit for purpose satisfies the needs of the client and produces results which can be used for their intended purpose, such as within a legal process

Formal Experimental Design / Design of Experiments - A structured, organized method for determining the relationship between factors affecting a process and the output of that process

G

Good Engineering Practices (GEP) - Established engineering methods and standards that are applied throughout the project life-cycle to deliver appropriate, cost-effective solutions.

Good Laboratory Practice (GLP) - Good Laboratory Practice is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

Good Manufacturing Practice (GMP) - All elements in the established practice that will collectively lead to final products or services that consistently meet appropriate specifications and compliance with national and international regulations.

Goodness-of-Fit - How well a model, a theoretical distribution, or an equation matches actual data

Gowning Qualification- A program that establishes, both initially and on a periodic basis, the capability of an individual to don the complete sterile gown in an aseptic manner

H

Harm - Damage to health, including the damage that can occur from loss of product quality or availability.

Harmonization - Bringing about agreement on terminology, concepts, etc. so that different entities can interact based on the same terms of reference

Hazard - The potential source of harm

HEPA Filter - High efficiency particulate air filter with minimum 0.3 μm particle retaining efficiency of 99.97 percent. To achieve an appropriate cleanliness in the premises, High efficiency particulate air (HEPA) filters are used. The HEPA filters are employed to ensure the aseptic condition. The integrity of the filters should be checked at regular intervals by performing leak test. HEPA filters are a part of the air handling unit (AHU).

Heating, Ventilation, and Air conditioning (HVAC) - HVAC encompasses heating, ventilation, and air conditioning, which is integral component of pharmaceutical facility functionality. The system is needed for maintenance of a suitable temperature, for continuous flow of air, which ultimately prevents cross?contamination and accumulation of air and to ensure the cooling of air in the premises.

Homogeneity - A material is regarded as homogeneous when it is all of the same origin (e.g. from the same batch) and as non-homogeneous when it is of differing origins

Hypothesis testing or Significance testing – It is the process of assessing the statistical significance of findings. It involves comparing empirically observed sample findings with theoretically expected findings, expected if the null hypothesis is true

This comparison allows one to compute the probability that the observed outcomes could have been due to chance alone.

Alternative Hypothesis - Hypothesis that must be accepted if the null hypothesis is rejected.

Null Hypothesis(Ho) - Any hypothesis to be tested. The term null implies that there is no difference between the observed and known values other than that which can be attributed to random variation

I

Impurity - Any component of the drug substance that is not the entity defined as the active ingredient or a concomitant component, but is present as a consequence of either the raw materials used or the manufacturing process and is not a foreign substance.

Impurity Profile - A description of the identified and unidentified impurities, and their acceptance criteria, present in a drug substance

Indirect Impact System - This is a system that is not expected to have a direct impact on product quality, but typically will support a direct impact system. These systems are designed and commissioned according to GEP only.

Independent Test Result - Result obtained in a manner not influenced by any previous results on the same or similar material

Influence Quantity - Quantity which is not the subject of measurement but which influences the result, e.g. environmental conditions

Installation Qualification (IQ) - The performance and documentation of tests to ensure that equipment (such as machines, measuring equipment) used in a manufacturing process, are appropriately selected, correctly installed and work in accordance with established specifications.

Instrument (Instrumentation, Measuring Instrument) - Device intended to make a measurement, alone or in conjunction with other equipment.

Instrument Linearity - Straight-line relationship between analyte concentrations and the instrument response, in which a change in concentration causes a proportional change in response.

Instrument Validation - Process of establishing that an instrument at any given moment is able to perform according to its design specification This process might be achieved for example by means of calibration or performance checks

Interference Study - Study to check the selectivity (or specificity) of a method by adding materials which might be encountered in specimens and which it is suspected might cause interference.

Interfering Substance - Substances other than the analyte that give a similar analytical response or alter the analytical result

Internal Standard - Compound added to a sample in known concentration to facilitate the qualitative identification and/or quantitative determination of the sample components. The physicochemical characteristics of the internal standard should be as close as possible to those of the analyte, for example, a structurally similar analogue or a stable isotope-labelled analogue of the analyte can be used

International Standard - Standard recognized by an international agreement to serve internationally as the basis for fixing the value of all other standards of the quantity concerned

Interpretation - Explanation of what analytical results mean based on chemical, pharmacological, toxicological and statistical principles.

Intralaboratory Test Comparisons - Organization, performance and evaluation of tests on the same or similar items or materials within the same laboratory in accordance with predetermined conditions

Intervention- An aseptic manipulation or activity that occurs at the critical area

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 specifications. The control of the environment or equipment may also be regarded as a part of in-process control.

Intermediate product - Partly processed product that must undergo further manufacturing steps before it becomes a bulk product

Infiltration - Infiltration is the ingress of air from an external zone into a controlled area

ISO 14644-1 - International standard relating to the classification of clean environments. It is set to replace all existing national standards such as the US Fed. Std. 209, BSS5295, EEC and DIN. This guideline will make reference to the ISO classifications.

Isolator- A decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality, that provides uncompromised, continuous isolation of its interior from the external environment (e.g., surrounding cleanroom air and personnel).

There are two major types of isolators:

i) Closed isolator systems exclude external contamination from the isolator’s interior by accomplishing material transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding environment. Closed systems remain sealed throughout operations.

ii) Open isolator systems are designed to allow for the continuous or semi-continuous ingress and/or egress of materials during operations through one or more openings. Openings are engineered (e.g., using continuous overpressure) to exclude the entry of external contamination into the isolator

L

Laboratory - Facilities where analyses are performed by qualified personal and with adequate equipment

Laboratory Manager - Qualified individual who assumes professional, organizational, educational and administrative responsibility for the laboratory’s drug testing

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

Large-Volume Parenterals - Sterile solutions intended for parenteral application with a volume of 100ml or more in one container of the finished dosage form.

Least-squares - Statistical method of determining a regression equation, that is, the equation that best represents the relationship among the variables

Level of Significance - Probability that a result would be produced by chance alone, i.e. the probability of incorrectly rejecting the null hypothesis. It is therefore the probability of making a type I error

Licensee - Licensee is the person or business that has the primary responsibility for the supply. The Licensee could be the manufacturer, importer, distributor or the certificate holder of a pharmaceutical product

Limit - Prescribed or specified maximum or minimum amount, quantity or number

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

Limit of Quantitation (LOQ) - The lowest amount of analyte in a sample which can be quantitatively determined with defined precision and accuracy under the stated experimental conditions.

Limiting Mean - Asymptotic value or population mean of the distribution that characterizes the measured quantity; the value that is approached as the number of observations approaches infinity

LIMS (Laboratory Information Management System) - Software package for collating, calculating, controlling and disseminating analytical data. It can perform a variety of functions, from specimen registration and tracking; to processing captured data, quality control, financial control and report generation

Linear Regression - Method of describing the relationship between two or more variables by calculating a “best fitting” straight line or graph

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.

Logbook - Book which records laboratory activities, e.g. instrumentation, maintenance of instrumentation, sample preparation and reagents

M

Maintenance - Activity of keeping something such as facilities, machines or instrumentation in good condition by regularly checking it and doing necessary repairs.

Management Review - Scheduled review of the laboratory’s quality management system and its testing activities organized by the quality manager to ensure that they remain suitable and effective or to identify any changes and improvements required. The review should be carried out by high-level management of the organization of which the laboratory is a part, the quality manager and other relevant staff.

Management Structure - Hierarchy of personnel in an organization. This is often portrayed in an organigram or tree diagram

Matrix - Material which contains the analyte e.g. urine, blood etc.

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

Material Flow – The flow of material and personnel entering controlled environments should follow a specified and documented pathway that has been chosen to reduce or minimize the potential for microbial contamination of the product/closure/container systems. Deviation from the prescribed flow could result in increase in potential for microbial contamination. Material/personnel flow can be changes but the consequences of the changes from a microbiological point of view should be assessed by responsible managers and must be authorized and documented.   

Manufacture - All operations of purchase of materials and products, production, quality control, release, storage and distribution of pharmaceutical products, and the related controls.

Manufacturer - A company that carries out operations such as production, packaging, repackaging, labelling and relabelling of pharmaceuticals.

Marketing authorization / Product License, Registration Certificate - A legal document issued by the competent drug regulatory authority that establishes the detailed composition and formulation of the product and the pharmacopoeial or other recognized specifications of its ingredients and of the final product itself, and includes details of packaging, labelling and shelf-life.

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

Master Record - A document or set of documents that serve as a basis for the batch documentation (blank batch record)

Master Schedule - Compilation of information to assist in the assessment of workload and for the tracking of studies at a test facility

Measurand - Particular quantity subject to measurement

Specification of a measurand may require statements about quantities such as time, temperature and pressure.

Measurement- Set of operations having the object of determining a value of a quantity.

Measurement Procedure - Set of operations, described specifically, used in the performance of measurements according to a given method

Media Blank - An unexposed sampler, not taken to the field or shipped, used for background correction of sample readings or for recovery studies.

Media Growth Promotion – Procedure that references Growth Promotion under Sterility tests to demonstrate that media used in the microbiological monitoring program or in media fill runs are capable of supporting growth of indicator microorganisms and of environmental isolates from samples obtained through the monitoring program.

Media Fill – Microbiological simulation of an aseptic process by the use of growth media processed in a manner similar to the processing of the product and with the same container/closure system being used.

Median - Middle value of a ranked set of data

Metabolite - Compound produced in the body as a result of biochemical processes.

Method - A comprehensive description of all procedures used in sample analysis.

Method Authorization Form - Document which certifies that an analytical method has been validated for its intended purpose in the laboratory and has been authorized for that purpose by the laboratory manager, who should sign the form

Method of Measurement - Logical sequence of operations, described generically, used in the performance of measurements.

Method Scope - Circumstances or conditions under which a method will produce valid analytical results. This statement is usually contained in the standard operating procedure for the method and will refer to the analytes included, sample matrix type(s), concentration range, known interferences, etc.

Method Traceability - Property of the result of a measurement or the value of a standard whereby it can be related, with a stated uncertainty, to stated references, usually national or international standards, through an unbroken chain of comparisons.

Method Validation - Confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use of a method are fulfilled. Also defined as the process of verifying that a method is fit for purpose, i.e. for the use of solving a particular analytical problem or as the process by which it is established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical application.

Mode (Statistic) - Value or values occurring most frequently in a set of data

Mean kinetic temperature - The single test temperature for a drug product corresponding to the effects on chemical reaction kinetics of a given temperature-time distribution. A mean kinetic temperature is calculated for each of the four world climatic zones according to the formula developed by Haynes (2). It is normally higher than the arithmetic mean temperature.

N

National Standard - Standard recognized by an official national decision as the basis for fixing the value, in a country, of all other standards of the quantity concerned.

Negative - Indicates that the analyte is absent or below a designated cut-off. “Not detected” is sometimes used as a synonym of negative although this is not recommended

Negative Predictive Value - Number of negative results obtained by new method divided by number of true negative results

Non-conformance (non-conformity) - When the work carried out by the laboratory is inconsistent with its Quality Management System (for example, the work deviates from an operating procedure) or the requirements of its clients, this is termed a “non-conformance” in ISO 17025.

None Detected - Indicates the absence of an analyte within the specifications of the test(s) performed

Non-Parametric Test - Statistical method that makes no assumptions about the shape of the distribution of the population from which the sample data are taken

No Impact System - This is a system that will not have any impact, either directly or indirectly, on product quality. These systems are designed and commissioned according to GEP only.

Non-critical Parameter or Component - A processing parameter or component within a system where the operation, contact, data control, alarm or failure will have an indirect impact or no impact on the quality of the product

Normal Operating Range - Normal operating range is the range that the manufacturer selects as the acceptable values for a parameter during normal operations. This range must be within the operating range

O

Occurrence - Probability of negative events within a fixed time frame

One Point Calibration - Simplified calibration procedure using a single calibrator and a blank

Ongoing Validation - Control activities of the method characterize that taken during on going testing to approve the method control and that the validation results are valid.

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

Operational Qualification (OQ) - Documented verification that the system or sub-system performs as intended throughout all anticipated operating ranges.

Operating Limits - The minimum and/or maximum values that will ensure that product and safety requirements are met

Operating Range - Operating range is the range of validated critical parameters within which acceptable products can be manufactured.

Operational Condition - This condition relates to carrying out room classification tests with the normal production process with equipment in operation, and the normal staff present in the room.

Original Sample - Sample collected directly from the material

Organization - Companies, corporations or institutes (or part of e.g. laboratory) private or public, that has its own functions and administration. Some of the international organizations dealing with quality assurance (QA) are: The International Association of Forensic Toxicologists (TIAFT), The International Federation of Clinical Chemistry (IFCC), the International Olympic Committee (IOC), The International Organization for Standardization (ISO), The International Programme on Chemical Safety (IPCS), The International Union of Pure and Applied Chemistry (IUPAC) and the Organisation for Economic Cooperation and Development (OECD).

OSD - Oral Solid Dosage – usually referring to an OSD plant that manufactures medicinal products such as tablets, capsules and powders to be taken orally

Out of Specification Event – temporary or continuous event when one or more of the requirements included in standard operating procedures for controlled environments are not fulfilled.

Outlier - Result that appears to differ unreasonably from the population of the other results. Tests for outliers include:

i) Cochran test - This compares the largest of a set of variances with the other variances in the set

ii) Dixon Test - This compares the difference between a measurement and the one nearest to the measurement in size with the difference between the highest and lowest measurements in the set.

iii) Grubbs Test - Test for outliers which is now recommended to replace the Dixon test and to be used sequentially after the Dixon test. The single Grubbs test statistic is calculated as the percentage decrease in the standard deviation of a set of results following the removal of either the highest or lowest value in the set, whichever gives the largest decrease in the standard deviation. The pair Grubbs statistic is calculated in an analogous manner by removing the two highest, two lowest or else both the highest and the lowest values in the original set of results, whichever gives the lowest standard deviation. The presence of an outlier or a Grubbs outlier pair is indicated if the Grubbs statistic exceeds a critical value, which depends on the number of results in the set and which is given by a reference table.

Overkill Sterilization Process- A process that is sufficient to provide at least a 12 log reduction of microorganisms having a minimum D value of 1 minute

P

Packaging - All operations, including filling and labelling, that a bulk product has to undergo in order to become a finished product. Filling of a sterile product under aseptic conditions or a product intended to be terminally sterilized, would not normally be regarded as part of packaging.

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

Passive Systems - Systems which maintain a temperature-controlled environment inside an insulated enclosure, with or without thermostatic regulation, using a finite amount of pre-conditioned coolant in the form of chilled or frozen gel packs, phase change materials, dry ice or others

Pass - Through-Hatch (PTH) or Pass Box (PB) - A cabinet with two or more doors for passing equipment or product, whilst maintaining the pressure cascade and segregation between two controlled zones. A passive PTH has no air supply or extract. A dynamic PTH has an air supply into the chamber

Parametric Test - Statistical techniques designed for use when data have certain characteristics, usually when they approximate a normal distribution and are measurable

Peer - Individual having similar expertise in a relevant and specific functional area gained through documented training and expertise.

Peer Review - Review of casework for technical correctness by a peer.

Performance Qualification (PQ) - Documented verification that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters for prolonged periods (In the context of systems, the term “process validation” may also be used.)

Performance Indicators - Measurable values used to quantify quality objectives to reflect the performance of an organization, process or system, also known as performance metrics in some regions. (ICH Q10)

Personnel - Persons qualified, (at different levels, and sufficient in number) with adequate training and experience to carry out their assigned functions

Pests - Includes birds, bats, rodents and insects whose uncontrolled presence affects hygiene and cleanliness.

Pharmaceutical Product - Any material or product intended for human or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in the exporting state and/or the importing state.

Pharmaceutical Product Target Profile (PPTP) - A definition of the target properties of the FPP, including dosage form and strength(s), route of administration and relevant drug release and pharmacokinetic requirements.

Pharmaceutical Quality System - Management system to direct and control a pharmaceutical company with regard to quality

Pilot Scale - The manufacturing of a drug substance on a reduced scale by processes representative of and simulating those to be applied on a larger, production manufacturing scale

Piping & Instrument Diagrams (P&IDs) - Engineering schematic drawings that provide details of the interrelationship of equipment, services, material flows, plant controls and alarms. The P&ID also provide the reference for each tag or label used for identification.

Plant Functional Specifications - Specifications that document functions, standards and permitted tolerances of systems (plant) or system components (equipment) and which define the operating capabilities of the equipment.

Planned Risk Assessment - An assessment that is conducted in advance of an activity, either before any work is conducted or before further work is conducted. This enables quality to be built into activities and risk to be reduced, e.g. design of high containment facilities for manufacture of cytotoxic products.

Plot - Representation of data on or by a graph

Point Extraction - Air extraction to remove dust with the extraction point located as close as possible to the source of the dust

Population (or universe) - (Theoretical) Entity defined as an entire group of people, things, or events that have at least one trait in common.

Population Statistics - Statistical descriptors of the population, e.g. mean, median, mode, standard deviation, etc.

Positive - Indicates that the analyte is present at a level above a designated cut-off concentration.

Positive Predictive Value - Number of positive results obtained by a new method divided by number of true positive results.

Power of Test - Probability of rejecting the null hypothesis when it is false

Practicability - Ability to put something into practice. In the laboratory, this means the absence of unnecessarily sophisticated equipment, reagents, instruments, or environmental conditions, so that a method is suitable for routine use

Principal Investigator - Individual who, for a multi-site study, acts on behalf of the Study Director and has defined responsibility for delegated phases of the study. The Study Director’s responsibility for the overall conduct of the study cannot be delegated to the Principal Investigator(s); this includes approval of the study plan and its amendments, approval of the final report, and ensuring that all applicable Principles of Good Laboratory Practice are followed.

Precision - The repeatability or reproducibility of individual measurements expressed as standard deviation (SD), or relative standard deviation (CV).

Pressure Cascade - A process whereby air flows from one area, which is maintained at the highest pressure to another area at a lower pressure

Presumptive - This is used to describe things that are based on presumptions about what is probably true, rather than on certainty.

Presumptive Positive - Specimen or sample that has been flagged as positive by screening but which has not yet been confirmed by an adequately sensitive alternate chemical method.

Presumptive Negative - Specimen or sample that has been flagged as negative by screening. Usually no further tests are carried out and therefore there is no certainty about its content

Proficiency Testing - Any interlaboratory testing program where stable specimens are sent to participating laboratories for analysis. Results from all participating laboratories are compared, pooled, and tabulated by the testing program operator with the purpose of improving laboratory performance.

Proficiency Testing Scheme – It is an organized system for proficiency testing.

Probability - Mathematical measurement of how likely it is that something will happen, expressed as a fraction or percentage. Values for statistical probability range from 1 or 100% (always) to 0 or 0% (never). The relative frequency obtained after a long run of measurements or results will give good approximations to the true probability. Also, it is a basic concept which may be taken either as indefinable, expressing in some way a “degree of belief”, or as the limiting frequency of an occurrence in an infinite random series.

Probability Function - Function of a discrete variate that gives the probability that a specified value will occur

Process Robustness - Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality

Procedure - A detailed set of instructions (methodology) used to generate analytical data.

Prequalification - The activities undertaken in defining a product or service need, seeking expressions of interest from enterprises to supply the product or service, and examining the product or service offered against the specification and the facility where the product or service is prepared against common standards of good manufacturing practice (GMP). The examination of the product or service and of the facility where it is manufactured is performed by trained and qualified inspectors against common standards. Once the product is approved, and the facility is approved for the delivery of the specified product or service, other procurement agencies are informed of the approval. Prequalification is required for all pharmaceutical products regardless of their composition and place of manufacture or registration, but the amount and type of information requested from the supplier for use in the assessment by the procurement agency may differ

Processed Data - Information obtained from raw data in other to make it clear or more readily usable

Process Design - Defining the commercial manufacturing process based on knowledge gained through development and scale-up activities.

Process Validation - Documented verification that the integrated system functions as intended, in its normal operating environment. (The term Performance Qualification may be used also)

Process Qualification - Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing

Product Lifecycle - All phases in the life of the product from the initial development through marketing until the product’s discontinuation.

Product Contact Areas - Areas and surfaces in a controlled environment that are in direct contact with either products, containers, or closure and the microbiological status of which can result in potential microbial contamination of the product/container/ closure system. Once identified these areas should be tested more frequently than non- product contact areas or surfaces.

Pre-Determined Acceptance Criteria - The criteria assigned, before undertaking testing, to allow evaluation of test results to demonstrate compliance with a test phase of delivery requirement.

Primary Standard - Standard which has the highest metrological qualities in a specified field

Process Capability Study - A process capability study is a statistical method that compares process information (e.g. X and s) to the upper and lower specification limits.

Process Capability Index (CpK) - A process capability index CpK represents the true measure of process capability:

                        CpK = X – LSL / 3s

                                                (or)

                                    USL – X / 3S

LSL = Lower specification limit

USL = Upper specification limit

X = Mean

s = Standard deviation

Prospective Validation - Establishing documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol.

Protocol - Directive listing the procedures to be followed in performing a particular laboratory examination or operation—the overall plan analysis of a particular type of evidence

Production - All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing, packaging and repackaging, labelling and relabelling, to completion of the finished product.

Pressure Cascade - A process whereby air flows from one area, which is maintained at a higher pressure, to another area at a lower pressure

Pyrogen - A substance that induces a febrile reaction in a patient

Q

Qualitative Test - Test that determines the presence or absence of specific drugs or metabolites in the specimen or sample

Quality - The degree to which a set of inherent properties of a product, system, or process fulfils requirements.

Qualification - Identification of equipment attributes related to the performance of a particular function or functions and allocation of certain limits or restrictions to those attributes.

Quarantine - The status of starting or packaging materials, intermediates, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection or reprocessing.

Quality Audit - Systematic and independent examination to determine whether quality activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve the objectives

Quality Assessment - Overall system of monitoring activities which provides assurance that the quality control is performed effectively

Quality Assurance - It is a wide-ranging concept covering all matters that individually or collectively influences the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality assurance therefore incorporates GMP and other factors, including those outside the scope of this guide such as product design and development.

Quality Assurance Management - All activities of the overall management function that determine and implement quality policy, objectives and responsibilities

Quality Assurance Manager - Individual (however named) designated by top management who has the defined authority and obligation to ensure that the requirements of the quality assurance system are implemented and maintained.

Quality Assurance Programme - Internal control system designed to ascertain that the studies are in compliance with the principles of good laboratory practices (GLP).

Quality Critical Process Parameter - A process parameter which could have an impact on the critical quality attribute.

Quality Control Unit - Any person or organizational element designated by the firm to be responsible for the duties relating to quality control

Quality Management - That aspect of the overall management function that determines and implements the quality policy

Quality Management System (QMS) - Documentation of a laboratory’s policies, systems, procedures and instructions to the extent necessary to assure the quality of its results, to meet relevant jurisdictional, regulatory and safety requirements and to satisfy the needs of the clients. It covers the overall activities of the laboratory, including sampling, analysis and reporting, whether these are within the main laboratory facility itself, mobile/temporary facilities, or external locations such as a clandestine laboratory, the roadside, or the locus of a large drug seizure.

Quality Manual - Document stating the general quality policies, procedures and practices of an organization

Quality Policy - Statement by top management regarding the laboratory’s adherence to principles of quality. It may set forth codes of practice or ethics

Quality Standard - Typically, ISO17025, which is the quality standard specifically oriented towards laboratories undertaking chemical analysis. The standard lists a set of requirements which must be fulfilled in order for a laboratory to be accredited to the standard by an external accreditation body

Quality Risk Management - A systematic process for the assessment, control communication, and review of risks to the quality of the pharmaceutical product across the product life-cycle

Quality Monitoring – It is the part of a quality assurance program concerned with maintenance and improvement of quality which deals with the identification and use of indicators to detect variations from standards or specifications.

Quality Target Product Profile (QTPP) - A prospectively documented summary of the quality characteristics of a finished pharmaceutical product (FPP) that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the FPP. The QTPP forms the basis of design for the development of the product

Quantitation (Quantification) range - Range of concentrations, including ULOQ and LLOQ, that can be reliably and reproducibly quantified with accuracy and precision through the use of a concentration-response relationship

Quantitative Test - Test to determine the quantity of drug or metabolite present in a specimen

R

Random Sample - Sample in which the different fractions of the material have an equal probability of being represented

Range - 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.

Raw Material - Any ingredient intended for use in the production of APIs. These may include starting materials, process aids, solvents, and reagents.

Raw Data - All original test facility records and documentation or verified copies which are the result of the original observations and activities in a study. Raw data also may include, for example, photographs, microfilm or microfiche copies, computer readable media, dictated observations, recorded data from automated instruments, or any other data storage medium that has been recognized as capable of providing secure storage of information for a time period

Recall - A company’s removal or correction of its marketed drug substance that the USP Drug Substance SQP, an official organization such as the FDA, or the company initiates due to a critical drug substance deficiency

Reference Material - A generic term that refers to a material or substance whose property values are sufficiently homogeneous and stable with respect to one or more specified properties, and whose fitness is well established for its intended use in a measurement process

Reference Method/ Standard Consensus Method – It is a method developed by organizations or groups that use collaborative studies or similar approaches to validate them. Its value depends on the authority of the organizations which sponsor it

Reference Preparation - Processed reference material

Reference Standard - Standard, generally of the highest quality available at a given location, from which measurements made at that location are derived

Reference Value / Assigned Value - The quantitative or qualitative value that is assigned (accepted by convention as being the true value with known and acceptable uncertainty) to a Control Test Sample or primary standards.

Regression Analysis - Method of explaining or predicting the variability of a dependent variable using information about one or more independent variables.

Regression Curve - Curve that comes closest to approximating a distribution of points in a scatter diagram

Relative Frequency - Number calculated by dividing the number of values with a certain characteristic by the total number of values. It is also the frequency of an event which would occur in the long run given the probability of the event

Reliability - Extent to which an experiment, test, or measuring procedure yields accurate results in repeated trials

Reproducibility - The precision of the procedure when it is performed under different conditions.

Repeatability - Closeness of the agreement between the results of successive measurements of the same analyte made under repeatable conditions, e.g. same method, same material, same operator, same laboratory, narrow time period. Results should be expressed in terms of the repeatability standard deviation, repeatability coefficient of variation, or the confidence interval of the mean value.

Repeatability (of a measuring instrument) - Ability of a measuring instrument to provide closely similar indications for repeated applications of the same measurand under the same conditions of measurement.

Replicate analysis - Multiple analysis of separate portions of a test material using the same test method under the same conditions e.g. same operator, same apparatus, same laboratory

Representative Sample - Sample obtained according to a sampling procedure designed to ensure that the different parts of a batch or the different properties of a non-uniform material are proportionately represented.

Retention Sample - Sample collected as part of the original sampling process and reserved for future testing. The size of a retention sample should be sufficient to allow for at least two confirmatory analyses. In some cases statutory regulations may require one or more retention samples, each of which should be separately identified, packaged and sealed

Real-time (long-term) Stability Studies - Experiments on the physical, chemical, biological, biopharmaceutical and microbiological characteristics of a drug, during and beyond the expected shelf-life and storage periods of samples under the storage conditions expected in the intended market. The results are used to establish the shelf-life, to confirm the projected shelf-life, and to recommend storage conditions

Reconciliation - A comparison between the theoretical quantity and the actual quantity.

Recovery - The introduction of all or part of previous batches (or of redistilled solvents and similar products) of the required quality into another batch at a defined stage of manufacture. It includes the removal of impurities from waste to obtain a pure substance or the recovery of used materials for a separate use.

Refrigeration Equipment - The term “refrigeration” or “refrigeration equipment” means any equipment whose purpose is to lower air and product temperatures and/or to control relative humidity.

Relative Humidity - The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of the air at the same temperature expressed as a percentage. More simply put, it is the ratio of the mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given temperature.

Reprocessing - Subjecting all or part of a batch or lot of an in-process drug, bulk process intermediate (final biological bulk intermediate) or bulk 44 product of a single batch/lot to a previous step in the validated manufacturing process due to failure to meet predetermined specifications. Reprocessing procedures are foreseen as occasionally necessary for biological drugs and, in such cases, are validated and pre-approved as part of the marketing authorization.

Report - Document containing a formal statement of results of tests carried out by a laboratory. It should include the information necessary for the interpretation of the test results

Residual Solvents – They are the organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. They are not completely removed by practical manufacturing techniques.

Resolution - Ability to distinguish meaningfully between closely adjacent values

Response Time - Time interval between the instant when a stimulus is subjected to specified abrupt change and the instant when the response reaches and remains within specified limits of its final steady value.

Result - Information obtained from a test or series of tests. Usually it refers to processed data.

Result of a Measurement - Value attributed to a measurand, obtained by measurement. When the term is used, it should be made clear whether it refers to the indication, the uncorrected result, the corrected result, and whether several values are averaged. A complete statement of the result of a measurement includes information about the uncertainty of measurement.

Restricted Access Barrier System (RABS) - An enclosure that relies on HEPA filtered air over-spill to maintain separation between aseptically gowned personnel and operating environment. It is subject to a high level of disinfection prior to use in aseptic process. It uses decontaminated (where necessary) interfaces or RTPs for materials transfer. It allows for the ingress and/or egress of materials through defined openings that have been designed and validated to preclude the transfer of contamination. If opened subsequent to decontamination, its performance capability is adversely impacted.

Retest Date - The interval of time for which the drug substance must conform to applicable specifications when stored under labeled conditions. The retest date should be supported by stability data and be indicated on the drug substance label and exterior commercial packaging.

Reworking - Subjecting an in-process or bulk process intermediate (final biological bulk intermediate) or final product of a single batch to an alternate manufacturing process due to a failure to meet predetermined specifications. Reworking is an unexpected occurrence and is not pre-approved as part of the marketing authorization.

Retrospective Validation - Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data.

Re-Validation - A repeat of the process validation to provide an assurance that changes in the process/equipment introduced in accordance with change control procedures do not adversely affect process characteristics and product quality.

Review - Evaluation of laboratory results to ensure that they have been correctly interpreted

Risk - Combination of the probability of occurrence of harm and severity of the harm.

Risk Analysis - The estimation of the risk associated with the identified hazards.

Risk Assessment – It is a systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the evaluation of risk associated with exposure to those hazards.

Risk Control - The sharing of information about risk and risk management between the decision maker and other stakeholders

Risk Evaluation - The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk.

Risk Identification - The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.

Risk Priority Number (RPN) - A numeric assessment of risk assigned to a process, or steps in a process, as part of failure mode effects analysis (FMEA). Each failure mode gets a numeric score that quantifies likelihood of occurrence, likelihood of detection and severity of impact. The product of these three scores is the RPN for that failure mode.

RPN = severity rating × occurrence rating × detection rating.

Risk Review - Review or monitoring of output or results of the risk management process considering (if appropriate) new knowledge and experience about the risk.

Robustness – It is the ability to provide accurate and precise results under a variety of conditions.

Ruggedness - Partial or complete analysis of variance using experiments in which operational parameters of a sampling and measurement methods are varied within a small range to determine their effect on overall variance.

Ruggedness Test - Intralaboratory experimental plan, used before undertaking an interlaboratory study, to examine the behavior of an analytical process when small changes in the environmental and/or operating conditions are made, akin to those likely to arise in different laboratories

S

Safety Manager - Individual (however named) designated by top management who, irrespective of other responsibilities, has the defined authority and obligation to ensure that the requirements of the safety system are implemented and maintained.

Safety Manual - Document stating the safety policy and describing the various elements of the safety system of an organization

Sample - One or more parts taken from a system and intended to provide information on the system, often to serve as a basis for decision on the system or its production.

Sampler - Person responsible for performing the sampling operations

Sampling - Analytically, it is the whole set of operations needed to obtain a sample or specimen including planning, collecting, recording, labelling, sealing, shipping, etc. Statistically it is the process of determining properties of the whole population by collecting and analyzing data from a representative segment of it

Sampling Plan – A documented plan that describes the procedures and methods for sampling a controlled environment; identifies the sampling sites, the sampling frequency and number of samples; and describes the method of analysis and how to interpret the results

Sample Statistics - Statistical descriptors of the sample, e.g. mean, median, mode, standard deviation, range or size

Sampling Sites - Documented geographical location within a controlled environment, where sampling for microbiological evaluation is taken. In general, sampling sites are selected because of their potential for product/container/closure contacts.

Sampling Method - That part of the sampling procedure dealing with the method prescribed for withdrawing samples.

Scatter Diagram or Scatter Plot or Scattergram - Pattern of points that results from plotting two variables on a graph. Each point or dot represents one subject or unit of analysis and is formed by the intersection of the values of the two variables

Screening test or Initial test or Presumptive test - First test carried out on a specimen for the purpose of determining a presumption of a positive or negative assay. Usually presumptive positives are followed by a confirmatory test

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

Self-Contained Area - Premises which provide complete and total separation of all aspects of an operation, including personnel and equipment movement, with well established procedures, controls and monitoring This includes physical barriers as well as separate air-handling systems, but does not necessarily imply two distinct and separate buildings.

Service Level Agreement (SLA) - A service level agreement or contract is a negotiated agreement between the customer and service provider that defines the common understanding about materials or service quality specifications, responsibilities, guarantees and communication mechanisms. It can either be legally binding, or an information agreement. The SLA may also specify the target and minimum level performance, operation or other service attributes

Sensitivity - Capacity of the test procedure to record small variations in concentration of a component, with a defined degree of precision.

Shelf-Life - The period of time during which a drug product, when stored under the specified conditions, is expected to comply with the specification1 as determined by stability studies on a number of batches of the product. The shelf-life is used to establish the expiry date of each batch

Short-Term Study - A study of short duration with widely used, routine techniques

Simulated Product - A material that closely approximates the physical and, where practical, the chemical characteristics (e.g. viscosity, particle size, pH etc.) of the product under validation. In many cases, these characteristics may be satisfied by a placebo product batch.

Signal - Reported information (at least 3 spontaneous case reports) on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously.

Significant Figures - Number of figures that are consistent with the precision of the test

Skewness - Measures or scores that are bunched on one side of a central tendency parameter (mean, median, mode) and trail out on the other. The more skewness in a distribution, the more variability in the scores.

Specification - A list of detailed requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation.

Specificity - The degree of uniformity of the response to the substance in question

Specimen - Any material derived from a test system for examination, analysis, or retention.

Spike - A known mass of analyte added to a sampler for the purpose of determining recovery (analyst spikes), or for quality control (blind spikes).

Split-Level Model - Statistical model that splits the study sample according to a predetermined assumption so that only a portion of the cases falls into the category of interest, e.g. so that only some of the specimens that were positive for group A of drugs will be positive for group B.

Split Specimen or Sample - Practice of dividing a specimen or sample

Sponsor - An entity which commissions, supports and/or submits a non-clinical health and environmental safety study

Stability - The ability of a pharmaceutical product is to retain its chemical, physical, microbiological and biopharmaceutical properties within specified limits throughout its shelf life.

Standard Addition - Addition of a known amount of a pure component supposed to be present as a constituent of the specimen or sample in order to verify and quantitate this component

Standard Analyte - Well-defined substance in its highest available purity to be used as a reference in the analysis

Standard Deviation - Statistic that shows the spread or dispersion of scores in a distribution of scores. It is calculated by taking the square root of the variance. It is applicable to all kinds of repeated measurements, e.g. between-batch, within-batch, repeatability and reproducibility

Standard Solution: Solution of known concentration prepared from characterized material.

Statistical Control - A procedure is in statistical control when results consistently fall within established control limits, that is, with constant mean and variance. Statistical control should be monitored graphically with control charts.

Statistical Correlation - Extent to which two or more things are related to one another. This is usually expressed as a correlation coefficient.

Statistical Significance - A value or measure of a variable when it is larger or smaller than would be expected by chance alone. Statistical significance does not necessarily imply practical significance.

State of Control - A condition in which the set of controls consistently provides assurance of continued process performance and product quality.

Stability Tests - A series of tests designed to obtain information on the stability of a pharmaceutical product in order to define its shelf-life and utilization period under specified packaging and storage conditions.

Standard Operating Procedure (SOP) - An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material like equipment operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection. Certain SOPs may be used to supplement product-specific master and batch production documentation.

Starting Material - Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials.

Stakeholder - Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Primary stakeholders are the patient, health-care professional, MRAs and the pharmaceutical industry.

Sterile Field – In aseptic processing or in other controlled environments, it is the space at the level of or above open product containers, closures or product itself where the potential for microbial contamination is highest.

Stock Solution - Concentrated standard solution used to prepare calibrators

Study - An experiment or set of experiments in which a test item is examined under laboratory conditions or in the environment to obtain data on its properties and/or its safety, intended for submission to appropriate regulatory authorities

Study Director - Individual responsible for the overall conduct of the nonclinical health and environmental safety study

Study Plan - A document which defines the objectives and experimental design for the conduct of the study, and includes any amendments.

Study plan amendment - An intended change to the study plan after the study initiation date.

Study Plan Deviation - An unintended departure from the study plan after the study initiation date.

Study Initiation Date - The date the Study Director signs the study plan.

Study Completion Date - The date the Study Director signs the final report

Stability Protocol - Documents describing the sample, test specifications, test intervals, conditions, and packaging used to determine the shelf-life.

Sterility – An article is deemed sterile when there is complete absence of viable microorganisms. Absolute sterility cannot be practically demonstrated without testing every article in a batch. Sterility is defined in probabilistic terms, where the likelihood of a contaminated article is acceptably remote

Sterile Product- For purposes of this guidance, sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product.

Sterilizing Grade filter - A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent.

Storage Temperature - The temperature range listed on the TTSPP label, and within the regulatory documentation, for long-term storage.

Storage Unit Temperature/Humidity Distribution - The range and pattern of temperatures and/or humidity within a temperature controlled storage unit during normal operation.

Supporting Stability data - Supplementary data, such as stability data on small-scale batches, related formulations, and products presented in containers other than those proposed for marketing, and scientific rationales that support the analytical procedures, the proposed retest period or the shelf-life and storage conditions.

Suspect Product - A TTSPP whose presentation and/or pharmacological formulation indicates that it has not been manufactured by the company named on the packaging. A TTSPP that shows visible or pharmacological evidence of tampering

Surveillance - Monitoring of certain activities to ensure that specified requirements have been fulfilled

Survey - Study conducted among organizations to compile information on their activities or performance

System Suitability Test - Validation of an analytical system (system suitability testing) tests a system against documented performance specifications, for a specific analytical method

Swabs – Devices provided that are used to sample irregular surfaces for determination of microbial status. The swab, generally composed of a stick with an absorbent extremity is moistened before sampling and used to sample a specified unit of a surface. The swab is then rinsed in sterile saline or other suitable menstruum and the contents plated on nutrient agar plates to obtain an estimate of the viable microbial load on that surface.

T

Technical Manager - Person with responsibility for specified technical operations, the provision of the resources needed to ensure the required quality of these operations, the investigation and resolution of technical problems, and the evaluation of instrument calibration and maintenance records

Technical Procedure - Documented operation (procedure) carried out in a laboratory by trained technical or scientific personnel.

Technical Review - Review of bench notes, data and other documents which form the basis for scientific conclusion.

Technique - Scientific principle that can be used to provide data on the composition of a material. It is unusual to apply a technique directly to a test sample, as extraction and other steps are frequently required. A technique is therefore used in the last step of an analytical method which is usually the end-determination or end-step determination

Test Item - An article that is the subject of a study.

Test Facility - Persons, premises and operational unit(s) that are necessary for conducting the non-clinical health and environmental safety study. For multi-site studies, those which are conducted at more than one site, the test facility comprises the site at which the Study Director is located and all individual test sites, which individually or collectively can be considered to be test facilities.

Test Facility Management - The person(s) who has the authority and formal responsibility for the organisation and functioning of the test facility according to these Principles of Good Laboratory Practice

Test Linearity - Ability within a given range to obtain test results directly proportional to the concentration (amount) of analyte in the specimen or sample

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 Site - The location(s) at which a phase(s) of a study is conducted

Test Site Management - Person(s) responsible for ensuring that the phase(s) of the study, for which he is responsible, are conducted according to these Principles of Good Laboratory Practice

Test System - Any biological, chemical or physical system or a combination thereof used in a study

Temperature - Controlled - Includes any environment in which the temperature is actively or passively controlled at a level different from that of the surrounding environment within precise predefined limits.

Temperature Excursion - An excursion event in which a TTSPP is exposed to temperatures outside the range(s) prescribed for storage and/or transport. Temperature ranges for storage and transport may be the same or different; they are determined by the product manufacturer, based on stability data.

Temperature Modified - Includes any environment in which the temperature is predictably maintained at a level different from that of the surrounding environment, but is not actively or passively controlled within precise predefined limits.

Threshold - Particular, significant amount, level, or limit, at which something begins to happen or take effect

Time and Temperature Sensitive Pharmaceutical Product (TTSPP) - Any pharmaceutical good or product which, when not stored or transported within predefined environmental conditions and/or within predefined time limits, is degraded to the extent that it no longer performs as originally intended.

Traceable Standard - Reference standard which also has the property of traceability. It will usually have a certificate of analysis giving details of the national or international standards used to determine its composition

Traceability - Ability to trace the history, application or location of an entity by means of recorded identification

Training Record - Record maintained for each member of staff of their education, qualifications and training together with a list of tasks they are competent to perform and authorized to carry out, for example, to perform particular types of test, to issue test reports, to give opinions and interpretations and to operate particular types of equipment

Trueness - The closeness of agreement between the average values obtained from a large series of test results and an accepted reference value.

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

Trend Analysis – Data from a routine microbial environmental monitoring program that can be related to time, shift, facility etc This information is periodically evaluated to establish the status or pattern of that program to ascertain whether it is under adequate control. A trend analysis is used to facilitate decision making for requalification of a controlled environment or for maintenance and sanitization schedules 

Transport Temperature Profile - Anticipated ambient temperature variation and duration to which a TTSPP may be exposed during transport.

Turbulent Flow - Turbulent flow, or non-unidirectional airflow, is air distribution that is introduced into the controlled space and then mixes with room air by means of induction.

U

Uncertainty of Measurement - Parameter, associated with the result of a measurement that characterizes the dispersion of the values that could reasonably be attributed to the measurement.

Unexpected Adverse Drug Reaction - An adverse reaction, the nature or severity of which is not mentioned in the summary of product characteristic or market authorization, or expected from characteristics of the drug.

ULPA Filter- Ultra-low penetration air filter with minimum 0.3 μm particle retaining efficiency of 99.999 percent

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

Uniformity - A starting material may be considered uniform when samples drawn from different layers do not show significant differences in the quality control tests which would result in non-conformity with specifications.

Unplanned Risk Assessment - An assessment that is conducted to assess the impact of a situation that has already occurred, e.g. impact of a deviation from normal ways of working

Upper Limit of Quantification (ULOQ) - Highest amount of an analyte in a sample that can be quantitatively determined with an acceptable level of precision and accuracy

Utilization Period - The period of time during which a reconstituted preparation or the finished dosage form in an opened multidose container can be used.

Utilization Factor - The percentage of the total volume available for storing TTSPPs that can reliably be achieved in practice, taking account of the types of stock-keeping unit (SKU), the types of load support system and the stock management systems used in the store.

V

Validation- 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.

Validation Master Plan - A document providing information on the company’s validation work programme. It should define details of and timescales for the validation work to be performed. Responsibilities relating to the plan should be stated.

Validated Method - Method whose performance characteristics meet the specifications required by the intended use of the analytical results. Some of the performance characteristics to be evaluated are limit of detection, limit of quantitation, linearity, precision, range, ruggedness, selectivity and specificity, and trueness.

Validation Parameters - Key aspects of an analytical method which are evaluated for the purposes of method development and validation, including accuracy (bias), linearity, limit of detection, limit of quantitation, range, recovery, repeatability, reproducibility, ruggedness, and specificity (selectivity)

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 Report (VR) - A document in which the records, results and evaluation of a completed validation programme are assembled and summarized. It may also contain proposals for the improvement of processes and/or equipment

Validity - The degree to which output reflects what it purports to reflect, i.e., input; the degree to which output is a function of known input and it alone.

Value - Expression of a quantity in terms of a number and an appropriate unit of measurement

Variable - Any quantity that varies. More precisely, a quantity which may take any one of a specified set of values

Variance - Statistic that shows the spread or dispersion of scores in a distribution of scores. It is calculated by the sum of the squares of the differences between the individual values of a set and the arithmetic mean of the set, divided by one less than the number of values

Variate - In contradistinction to a variable, a variate is a quantity which may take any of the values of a specified set with a specified relative frequency or probability. It is often known as a random variable

Variability - Spread or dispersion of scores in a group of scores; the tendency of each score to be unlike the others

Vehicle - Any agent which serves as a carrier used to mix, disperse, or solubilize the test item or reference item to facilitate the administration/application to the test system.

Verification - The application of methods, procedures, tests and other evaluations, in addition to monitoring, to determine compliance with the quality risk management activities.

W

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.

Working Standard Solutions - Standard solutions prepared by dilution of the stock solution containing the concentrations used to establish the calibration curve

Z

Z-Score - Number of standard derivation units that separate a value from its mean

Pharmaceutical industry, glossary, terms, definations

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