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PQM
2017.01.21 08:43 6,983 0

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Absorbent - A material which, due to an affinity for certain substances, extracts one or more of these substances from a liquid or gaseous medium it contacts, and which changes physically, chemically or both during the process.

Absorption -1] - A process by which a substance is taken up in bulk by a material (Absorbent) and held in pores or interstices in the interior of the material; as opposed to Adsorption. A process whereby a material extracts one or more substances present in an atmosphere, a mixture of gasses or liquids. It is accompanied by a physical and or chemical change in the material. Transportation of the products of digestion from the intestinal tract into the blood stream.

Accelerated Stability Test – A short-term stability study conducted under exaggerated (or stressed) conditions to increase the rate of chemical or physical degradation of a drug substance or drug product.

Acceptability Limits – A specific set of operating parameters that, if deviated from, render the product quality in question. The acceptability limits should be set at proven acceptable range values.

Acceptable Criteria – The standards a product or process must meet to successfully complete a test phase or to meet delivery requirements.

Acceptable Daily Exposure (ADE) – A dose that is unlikely to cause an adverse effect if an individual is exposed, by any route, at or below this dose every day for a life time.  By definition the ADE is protective of all populations by all routes of administration.

Acceptable Quality Level (AQL) – The maximum percent Non-conforming units (or the maximum number of nonconformities per 100 units) that, for purposes of sampling inspection, can be considered satisfactory as a process average. The AQL specifies acceptable numbers of defective items in a lot.

Acceptable Range – A range of values of a control or operating parameter bound by specific upper and lower limits.

Acceptance Sampling Testing – A process by which a random sample is drawn from a product lot, and on the basis of results of testing or inspection of the sample, a decision is made regarding the disposition of the lot.

Acceptance Testing – Formal testing conducted to determine whether or not a system satisfies its acceptance criteria. It is also used to determine whether or not to accept the system. (FIPS Publication 101, June 1993)

Accuracy – 1] - The degree of freedom from error, the degree of conformity to a standard, or the closeness of  test results obtained by that method to the true value. Accuracy is often expressed as the percentage recovery by the assay of known, added, amounts of analyte. Accuracy is a measure of the exactness of an analytical method.  (See Precision.) 2] The agreement between a measured value and an accepted or true value. The accepted value can be obtained from a specially prepared (spike) sample, results from another test method of known accuracy and Precision, or through reference material (standard) of known or generally accepted composition. 66 3] The agreement between an experimentally determined value and the accepted reference value. In chemical work, this term is frequently used to express freedom from bias, but in other fields it assumes a broader meaning as a joint index of precision and bias.

Action Levels – 1] - A specific set of operating parameters which, when reached, signal variations from normal operating conditions and require documented action in order to return the system or process to a State of Control. 2] Microbial action levels (or ranges) which, when exceeded, signal an apparent drift from normal operating conditions and which require action. 

Action Limits – 1] - Maximum (microbial, particulate, etc.) limits established with a specific course of action to be taken when samples are found to exceed those limits.1,3 2] The concentration of Viable or Non-Viable Particulates that describe the maximum established specifications for an area that, when exceeded, may adversely affect a product. Investigations and Corrective Actions should be taken following excursions from Action Limits. A series of excursions from Alert Limits may also be used as a basis for triggering an appropriate investigation and Corrective Actions. Alert Limits for Critical and Controlled Areas should reflect actual  processing conditions and should not exceed limits stated in (the reference material) for airborne Viable and Non-Viable Particulates.

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

Act of God – An occurrence beyond the control of, or avoidance by, human power; any accident produced by physical causes, such as a fire, flood, earthquake, etc. It generally will not terminate a contract or discharge the parties, unless provided for in the agreement.

Adsorbent – A material which has the ability to cause molecules of gases, liquids or solids to adhere to its internal surfaces without changing the adsorbent physically or chemically. Certain solid materials, such as silica gel and activated alumina, have this property.

Adsorption – 1] - A process in which a substance is bound at the surface of a material (adsorbent). The assimilation of gas, vapor or dissolved matter by the surface of a solid or a liquid. The action of a material extracting one or more substances present in an atmosphere or a mixture of gasses and liquids. It is associated with the materials surface adherence, and is not accompanied by physical or chemical changes.

Aerobic – Refers to the growth of microorganisms in the presence of free oxygen, usually at normal air concentrations.

Aerophilic – Similar to the term aerobic, it is growth depending on free oxygen or air; "aerobic fermentation".  A subset of this is microaerophilic meaning that the microbe requires oxygen to survive, but requires environments containing lower levels of oxygen than are present in the atmosphere.

Airborne Particulate Count (Total Particulate Count) – When a number of particles are specified, then it is the maximum allowable number of particles per cubic foot (particles/ft3) or cubic meter (M3) of air.

Airborne Viable Particle 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 (M3), or cubic foot (ft3) of air that is associated with the cleanliness class of a Controlled Environment based on the Airborne Particulate Count.

Air Changes – 1] - The frequency (minutes, hours, etc.) with which the air in a Controlled Environment is replaced. The air can be recirculated partially or totally replaced. A method of expressing the amount of air leakage into or out of a building or room in terms of the number of building volumes or room volumes exchanged.

Air-Generated DOP – An aerosol generated by blowing air through liquid DOP at room temperature. When generated with a Laskin-type nozzle, the approximate light-scattering mean droplet size is as follows: 99+% less than 3.0 µm 50+% less than 0.7 µm, 10+% less than 0.4 µm18,58,20, (See Thermally Generated DOP and Diotcyl Phthalate [DOP].)

Air Lock – Two air-tight doors with a space between them. They are used to access different Cleanroom levels and maintain the independent integrity of each level. Typically the doors are controlled so that only one door can be opened at a time.

Air Sampler – Device or Equipment used to sample a measured amount of air in a specified time in order to determine the particulate or microbiological status of air.

Alert Levels – 1] - A specific set of operating parameters which, when reached, signal potential variations from normal operating conditions. The Alert Level is within the proven acceptable range and, therefore, does not necessarily mean that product quality is threatened. Occasionally, the monitoring frequency of operation and maintenance should increase on the system or process. 2] Microbial quality levels or ranges that signal, when exceeded, a potential drift from normal operating conditions. It may not require action, but it may need to be monitored more closely than standard. 

Alert Limits – The concentration of Viable or Non-Viable Particulates in an environment that, when exceeded, signal a potential drift from normal operating conditions. A review of recent monitoring data and manufacturing practices should be conducted following such excursions to ensure that the manufacturing environment is still in control. Alert Limits for Critical and Controlled Areas should reflect actual processing conditions and should be set below Action Limits. This will allow an adequate response time to implement Corrective Action and address potential deteriorating environmental conditions. (See Alert Levels.)

Algorithm – A set of well-defined rules that list a sequence of operations for performing a specific task.

Anaerobic – Refers to the growth of some microorganisms in the absence of free oxygen.

Analog – Continuous signal having a voltage corresponding to a monitoring value.

Analysis of Covariance (ANCOVA) – An analytical method, used with quantitative variables, that adjusts for the presence of covariates before performing an analysis of variance on the groups being compared.

Analysis of Variance (ANOVA) – An analytical method that compares the means of groups by analyzing each group’s contribution to the overall uncertainty (the variance) of the data.

Anisokinetic Sampling – The condition of sampling in which the mean velocity of airflow entering a probe inlet differs from the mean velocity of the air stream being sampled. Because of Particle inertia, Anisokinetic Sampling can cause the concentration of particles in the sample to differ from the concentration of particles in the air being sampled.

Antibody – A defense protein, synthesized by the immune system of an organism. It binds specifically to the foreign molecule (Antigen) and thereby inactivates it.

Antigen – Any molecule whose entry into an organism provokes synthesis of an antibody or Immunoglobulin.

Antigen Capture – A process in which Antigen in solution is bound by Antibody immobilization on a solid surface (e.g., a Membrane).

Antiseptic – A chemical Germicide formulated for use on skin or tissue. It should not be used to decontaminate inanimate objects.The selection and use of Antiseptics are extensively discussed in Larson, E.; “APIC Guideline for Use of topical Antimicrobial Agents,” American Journal of Infection Control, 1988 . Antiseptics are registered and regulated by the FDA.

Application – Software specifically produced for the functional use of a computer system. Software written to perform a task on a computer.

Application Software – A program adapted to the specific requirements of a user for the purposes of data manipulation, data archiving or process control.

Approved Document (Approval) – A written document (protocol, technical report, procedure, test method, etc.) has been approved after it has been reviewed and signed by a pre-defined group of responsible individuals representing manufacturing, engineering, QC, R&D and QA/regulatory or their designates. (See Validation Committee.)

Architectural Review – See Design Review.

Archived Master – A software library which contains formally approved and released versions of software and documentation from which copies are made.

Area – Generally used to designate a portion of a building at a given level of protection or contamination control. Used to differentiate it from adjoining portions of different contamination levels. Sometimes used  interchangeably with “space” or “zone.”

As-Built Facility (or Cleanroom) – A Clean Room (Facility) that is complete and ready for operation. All services are connected and functional, but it does not have operating equipment and personnel. (See At–Rest Facility and Operational Facility.)

Ascites – Liquid accumulations in the peritoneal cavity. Used as a method of producing monoclonal antibodies.

Aseptic – A state of being free from pathogenic (infectious) organisms or septic materials. Often erroneously assumed to be “Sterile.”

Aseptic Filling – A process whereby a drug is sterilized separately then packaged in sterilized containers and closures in an Aseptic environment.

Aseptic Processing – A process that is designed to prevent the introduction of viable organisms into sterile components. It is also used after an intermediate process has rendered the bulk product, or its components, free from viable micro-organisms.

Aseptic Processing Area (APA) – A controlled environment, consisting of several zones, in which the air supply, facility, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels.

Aseptic Processing Simulation (APS) – a synonym for media fills. it is a means for establishing the capability of an aseptic process as performed using a growth medium.

As-Found Data – Data comparing the response of an instrument to known standards, as determined without adjustment, after the instrument is made operational.

Assembler – Software that translates assembly code to executable machine code.

Assurance – A measure of confidence that the security features and architecture (of a LIMS) accurately mediate and enforce the security policy.

Atopy – A clinical hypersensitive state, or allergy, with a hereditary predisposition; that is, development of some form of allergy is inherited, but the specific form it takes, such as hay fever, eczema and asthma, is not.

At-Rest Facility (or Cleanroom) – Is a Clean Room (Facility) that is complete with operating equipment installed, but without personnel. (See As-Built Facility and Operational Facility.)

Audit (Quality Audit) – 1] A documented activity performed on a periodic basis in accordance with written procedures to verify, by examination and evaluation of the objective evidence, compliance with those elements of a quality program under review. An independent review to assess compliance with requirements, specifications, baselines, standards, procedures, instructions, codes and contractual and licensing requirements. A qualitative and quantitative evaluation of the documentation and procedures associated with the LIMS to verify that any resulting LIMS Raw Data are of acceptable quality.

 

Backup – Provisions made for the recovery of data files or software. Used in a restart of processing, or in alternative computer equipment, after a system failure or a disaster.

Balance – The condition, in a study, in which all subgroups being analyzed have an equal number of subjects/patients.

Barrier System – A system of physical partitions that provides ISO 5 protection by partially separating its interior from the surrounding environment utilizing airflow.

Baseline – A group of configuration items (work products, deliverables) developed during a specific phase of the development process that have been formally accepted. Once the baseline is established, changes to the items can only be done through a formal change process.

Batch – A quantity produced according to a single manufacturing specification during the same manufacturing cycle.

Batch Processing – Execution of programs serially, with no interactive processing.

Baud – The rate at which data is received or transmitted in serial. For example one baud is one bit per second.

Beta Ray [Beta Particle] (ß+ and ß-) – An electron or positron emitted from a nucleus. Not as penetrating as a Gamma Ray.

Bias – A constant (or systematic) error, as opposed to a random error. It manifests as a persistent plus/minus deviation from the method average of the accepted reference value.

Binary – The Base Two number system. Permissible digits are 0 and 1.

Bioburden – The amount of naturally occurring bacteria present in or on a load (or items in a load) prior to a Sterilization process. Pre-sterilization bioburden is measured immediately before Sterilization and includes all surfaces or materials which will be sterilized, including inside surfaces of the primary package.

Bioburden-based Process – A Sterilization process based on anticipated levels of microbial contamination on all surfaces to be sterilized. A number of Bioburden measurements, made immediately before Sterilization, are used to establish the level (both mean and standard deviation) and resistance of microorganisms on the surfaces to be sterilized.

Biologic – A biologic is a virus, therapeutic serum, toxin, antitoxin or analogous product applicable to the prevention, treatment or cure of diseases or injuries of man. [PHS Act]

Biological Indicator (BI) – A carrier, or suspension, of a specific species of microorganism (bacteriologic Spores) with a high resistance to the particular mode of Sterilization being monitored. It may be contained in a package or delivery device designed to maintain the integrity of the inoculated carrier. The population is known and is higher than the expected naturally occurring Bioburden of the product. By integrating the effects of process conditions, BIs demonstrate the effectiveness of the Sterilization process.

Biological Oxygen Demand (BOD) – The oxygen used in meeting the metabolic needs of Aerobic organisms in water containing organic compounds.

Biological Safety Cabinet – Primary containment device in which work may be performed on infectious agents.

Biotechnology – The application of biological systems and organisms to technical and industrial processes.

Bit – 1] A contraction of the term binary digit. It is a unit of information represented by either a 0 or a 1.22. A single pulse in a group of pulses. 3] A unit of information capacity of a storage device. The capacity, in bits, is the logarithm to the base 2 of the number of possible states of the device. (Related to storage capacity.)

Bottom-Up – Pertaining to an approach that starts with the lowest level of software components in a hierarchy and proceeds through progressively higher levels up to the top component.

Buffer – Portion of memory used to temporarily hold data for further processing.

Bug – See Fault.

Bus – Electrical pathway information flows through to reach different devices.

Byte – 1] A generic term to indicate a measurable portion of consecutive bits (e.g., an 8-bit byte). A sequence of adjacent bits, usually shorter than a word, operated on as a unit. 3] A binary character string operated on as a single unit. The lowest addressable unit in a computer.

cGMP – Current Good Manufacturing Practice [i.e., Title 21, Code of Federal Regulations, Sections 210, 211, 212, 820, 600 series, etc.].
 
Calibration – Documented comparison, by written and approved procedures, of a traceable measurement standard, of a known accuracy, with another measuring device to respond to, detect, correlate, report or eliminate any variation in the accuracy of the item being compared over an appropriate range of measurements. This process results in documented adjustments or corrections that can be made if maximum accuracy is required.
 
Calibration Verification – The assaying of Calibration materials to confirm that the Calibration of the instrument, kit or test system has remained stable throughout the reportable range for test results. Performance and documentation of Calibration Verification is required to substantiate the continued accuracy of a quantitative test method for the reportable range of test results. (a.k.a. –  Verification of Accuracy.)
 
Calibrator – 1] A device intended for use in a test system to establish the points of reference for the determination of values in the measurement of the test instrument. 21 2] Special samples of known values specifically prepared to set up a standard curve, or cut-off point, of an assay. Used in the Calibration of a diagnostic assay. Requirements for method Calibration are outlined in 21 CFR 809.10(b)(8)(v).
 
Campaign – A series of consecutive production batches manufactured without intervening cleaning and sterilization.
Campaign Manufacturing – Processing of more than one product in the same facility and/or Equipment in a sequential manner. Only one product is present in any one manufacturing area of the facility at a time.
Capacity Requirement Planning (CPR) – A sub-system of MRP II that enables manufacturers to plan and schedule Equipment use and production.
 
Certification – 1] A documented statement, by authorized and qualified individuals (Validation Committee), that an equipment/system validation, revalidation, qualification, requalification or calibration has been performed appropriately with acceptable results. Certification may also be used to denote the overall acceptance of a newly validated manufacturing facility.A written guarantee that a system, instrument, test or computer program complies with its specified requirements.
 
Challenge – The performance of tests to determine the limits of capability of a component in a manufacturing process. Limits of capability do not necessarily mean challenging until destruction, but rather the limits of variation within which a defined level of quality can be assured.
 
Change Control – 1] A formal monitoring system by which qualified representatives (Validation Committee) of appropriate disciplines review proposed or actual changes that might effect a validated status. This is done to determine the need for Corrective Action to ensure that the system retains its validated state.Management and implementation methodologies associated with increasing or correcting system capabilities, a partial system redesign or the determining of software obsolescence.
 
Changeover – The process of preparing a piece of equipment, used for the production of a specific product, for the production of a different product. Changeover usually includes cleaning, sampling and testing to assure fitness for use in the next production process.
 
Characteristic – A physical, chemical, visual, functional or other identifiable property of a product, component or raw material.

Chemical Sterilants – Chemicals used for the purpose of destroying all forms of microbial life. This includes fungal and bacterial spores.

 
Chemiluminescent – Antigen or antibody reaction that results in the emission of light from a chemical or enzymatic reaction.

Chip – An electronic hardware component, consisting of integrated microcircuits, that performs a significant number of functions.

 
Chi-Square (x2) Test Method – A variance ratio test used to decide whether the observed variance is different from a known or established variance. This test is also used to determine if the observed number of occurrences of an event differs significantly from the expected number.
 
Clean Air Device – A small enclosure that has its own filtered air (or gas) supply. It may or may not be located in another controlled space (e.g., a Clean Room).
 
Cleaning – The removal of all foreign material (e.g., soil, organic material) form objects. It is normally accomplished with water, mechanical action and detergents. Cleaning must precede Disinfection and Sterilization processes.
Clean-in-Place (CIP) – The act of cleaning process equipment and/or systems (tanks, vessels, filling machines, distribution lines, etc.) without dismantling them.
 
Clean-Out-of-Place (COP) – The act of cleaning process equipment and/or systems (tanks, vessels, valves, filter housings, etc.) by dismantling and removing the component from its normal operational position for the purpose of cleaning. 
Clean Room (or Cleanroom) – 1] A specially constructed room in which the air supply, air distribution, filtration of air supply, materials of construction and operating procedures are regulated to control airborne particle concentrations in order to meet appropriate cleanliness levels as defined by Federal Standard 209E. 3, 20 2] A room in which the concentration of airborne particles, both Viable and Non-Viable, are controlled to specified limits. It may contain one or more Clean Zones. Clean Rooms fall into three categories; Laminar Air-Flow and Conventional or a combination of the two. If it is the combined form, the absolute air is supplied to the room in a turbulent manner (Conventional) and laminar-flow units or modules are placed directly above or in front of a Critical part of the process. 18 3] A room which is in control of particulate contamination and construction, and which is used in such a way as to minimize the introduction, generation and retention of particles inside the room. Temperature, humidity and pressure can be controlled as necessary.
Clean Zone – A defined space in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. (SeeControlled Area(s) and Critical Area(s).)
 
Closures – Those portions of drug or diagnostic systems, such as stoppers, caps or other barriers, which may be removed or otherwise altered in order to grant access to the container contents.

Cochran-Mantel-Haenzel Method – A Chi-Square method that permits statistical comparison of odds across subgroups and allows differences in those ratios to be adjusted.

 
Code – To represent data or a computer program in a symbolic form that can be accepted by a processor. Loosely, one or more computer programs, or part of a computer program.

Code Audit – An independent review of Source Code by a person or team of persons, or a tool to verify compliance with software design documentation and program standards.

 
Coefficient of Determination – The square of the correlation coefficient. It is the proportion of the variation in the dependent variable which is accounted for by the independent variable, and is usually expressed as a percentage.
 
Coefficient of Variation (CV) – A measure of relative Precision; defined as the sample standard deviation divided by the sample average and multiplied by 100.70 (a.k.a. Relative Standard Deviation.)

Cold – Any temperature not exceeding 8?C. A refrigerator is a Cold place in which the temperature is maintained thermostatically between 2?C and 8?C.

 
Colony – A growth of microorganisms on a solid medium. The growth is visible without magnification. A mycelial fungal Colony is a group of hyphae (with or without conidia) that arise from one Spore or cell.

Colony-Forming Unit (CFU) – That which results in the formation of a colony of microbial growth on appropriate solid media. Assumed to originate from one cell, but difficult to prove.

Combination Approach – The Combination Approach is the use of the Verification Approach until sufficient repeats of the cleaning procedure have been performed to consider the cleaning procedure to be Validated.

Commercially-Available Software – Software that is available through lease or purchase in the commercial market. Software that is furnished as part of the (LIMS) system that is separately priced, but included.

 
Commissioning – Putting a facility in a condition that is fit for use and ready for service. The Commissioning activity is conducted in parallel to the Validation (IQ/OQ/PQ) activity. Validation documents should be considered supplemental and complimentary to Commissioning documents, but duplication should be avoided. 55 (See Specification(s) Qualification.)

Commissioning of a Controlled Environment – Certification by engineering and quality control that an Environment has been built according to the specifications of the desired cleanliness class. Under normal operating conditions (or Worst-Case conditions) it is capable of delivering an Aseptic process. Commissioning includes media-fill runs and the results of the Environmental Monitoring Program.

 
Compile – To translate a higher order language program into its absolute machine code equivalent.
Complaint – Any written, electronic or oral communication that relates to or concerns the unacceptability of the identity, quality, durability, reliability, safety, effectiveness or performance of a device.
Component – Any material, substance, piece, part or assembly used during product manufacture intended to be in a finished product or device.

Computerized Numerical Control (CNC) – A system permitting manufacturers to control manufacturing equipment by means of data loaded into the equipment’s computerized memory.

Computer Program – A collection of logically interrelated statements or instructions that, when executed by a computer, makes possible the performance of a predefined task.

Computer System – A group of hardware components assembled to perform in conjunction with a set of software programs. Collectively, they are designed to perform a specific function or group of functions.

 
Concordance Correlation Coefficient (CCC) –  A statistical measurement that assesses the agreement between two variables so as to evaluate reproducibility of either an analytical method or process.
 
Concurrent Manufacturing – Concurrent Manufacturing in a Multiproduct Facility is characterized by the simultaneous production of a number of different products in segregated areas within the same facility.
Concurrent Validation – Established documentational evidence, based on an approved Validation Protocol, that a process does what it purports to do.This, in turn, is based on information generated during the actual operation and implementation of the process to make clinical or marketable product.
Condensation Nucleus Counter (CNC) – An instrument for counting small airborne particles, approximately 0.01 µm and larger, by optically detecting droplets formed by the condensation of a vapor on the particles.

Confidence Interval or Confidence Limits – These terms (usually expressed as a percentage; e.g., 95% confidence level) refer to “that interval or range of values around an observed value which will in 95% of the cases include the expected value. The expected value is defined as the average of an infinite series of such determinations.”

 
Confidence Level – This term (usually expressed as a percentage; e.g.,95% confidence level) is commonly used in establishing the probability of Precision statements and Means that there are used, (i.e.) 95-in-100 chances of being correct, and 5-in-100 chances of being wrong, in predicting that the expected Precision (or expected Value) will fall within the specific limits of the range.

Configuration – The arrangement of a load, system, computer system or network as defined by the nature, number and chief characteristics of its functional units. Configuration may refer to hardware or software.

Construction Qualification – 1] Documented evaluation of the construction or assembly of a piece of equipment or system to assure that it is in agreement with the approved specifications, applicable codes and regulations and good engineering practices. The conclusion of the construction qualification final report shall clearly state whether or not the equipment, process, system or facility is constructed in conformance with the approved specifications. 56 2] A process of monitoring the construction activities during their execution to verify their correctness.
 
Contamination Rate  The percentage of units filled in process simulation that are positive for microbial growth after incubation.
 
Continued Process Verification – Assuring that during routine production the process remains in a state of control. This is Stage 3 referenced in the FDA Guidance for Industry, Process Validation 2011.
 
Continuous Process Verification – An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated.
Control Number – A unique combination of letters, numbers or both that are assigned to a document. This can be used to determine the complete history (e.g., the purchasing, manufacture, control, packaging, labeling, servicing, maintenance, installation procedures and distribution) of a production run, lot or batch of a finished device or product.
 
Control Parameters – See Process Control Parameter.

Control Parameter Range – A range of values for a given Control Parameter that lies between its two outer limits or control levels.

 
Control Strategy – A planned set of controls, derived from current product and process understandingthat ensures process performance and product quality. The controls can includeparameters and attributes related to drug substance and drug 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.
 
Controlled Area(s) –  1] An area (of an Aseptic facility) where un-sterilized product, in-process materials and container/closures are prepared, including compounding, bulking and component preparation areas. This environment should be of a high microbial and particulate quality to minimize the level of particulate contaminants in the final product and to control the microbiological content (Bioburden) of articles and components that are subsequently sterilized. Air in Controlled Areas is generally of acceptable particulate quality if it has a per-cubic-foot particle count of not more than 100,000 in a size range of 0.5 µm and larger when measured in the vicinity of the exposed articles during periods of activity. 2] Also defined as a Class 100,000 area with no more than 25 CFU/10 ft3 (<87 CFU/M3) of air sampled. Surfaces should be at 323,000 CFU/M2 (3.23CFU/cm2 or 20 CFU/2 in2 )7A. 3] Also an area (of an Aseptic facility) where autoclaves are unloaded, materials are staged, sterilized items are transported is defined as a Class 1,000 (M2 or IS–M4.5) to 10,000 (grade y or M2 or IS–M5.5) area with <0.15 CFU/ft3 (or 5 CFU/M3) to 0.5 CFU/ft3 (or 18 CFU/M3) of air sampled.18 Surfaces should be at 5 CFU/2 in2. 7A Air Flows should be maintained at a rate to achieve 60-75 air-changes/ hour.
 
Controlled Environment – Any area in a process system for which airborne particulate and microorganism levels are controlled to specific levels appropriate to the activities conducted within that environment.

Controlled Room Temperature – A temperature maintained thermostatically that encompasses the usual and customary working environment of 20?C to 25?C (68?F to 77?F); that results in a mean kinetic temperature calculated to be not more than 25?C; and that allows for excursions between 15?C and 30?C (59? and 86?F) that are experienced in pharmacies, hospitals and warehouses. (See Stability under Pharmaceutiucal Dosage Forms <1151>. 14 See Room Temperature.)

 
Controlled Space – A Clean Zone of a Clean Room or Clean Air Device.

Conventional Clean Rooms – A room in which the air is supplied to the enclosure through terminal absolute filter modules in the ceiling or walls, and covering less than 80% of the cross-sectional area. Air delivered to the room is of a turbulent nature. 18 (See Table 1 and Table 2 Nonunidirectional Airflow.)

 
Cool – Any temperature between 8?C and 15?C. An article for which storage in a cool place is directed may be stored in a refrigerator unless otherwise specified.  (See Cold.)

Corrective Action – An action, specified in Standard Operating Procedures, that is taken in response to information gathered from environmental monitoring data. This may be implemented when Alert or Action Limits (Levels) are exceeded or when Trend Analysis indicates a developing problem. Actions taken should be commensurate with the severity of the excursion. Action to eliminate the cause of a detected non-conformity or other undesirable situation.

 
Correlation Coefficient – A measure of the degree of correlation between two variables. Values of “r” may range from -1 to +1. A value of +1 denotes a perfect functional relationship between the two variables, with an increasing value of one variable being associated with an increasing value of the second. A value of -1 also denotes a perfect relationship, but in this case an increasing value of one variable is associated with decreasing value of the second. If r = 0, then there is no effect of one variable on the other.

Count Reduction – An actual measurement of the number of surviving microorganisms after subjecting them to a known inoculum or a sterilization process.

 
Cox Regression Method – An analytical method in which event data for each group under comparison are transformed to fit a linear model. Models for each group are then compared to determine whether they are equal. This method assumes that hazard rates for each group are at least proportional to each other.

Critical – Of or pertaining to a condition causing an abrupt change in the quality or property of an Environment, process or product. (ISO is using the word Significant in place of the word Critical.)

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

Critical Component – Any component of a Critical Device who’s failure to perform can be reasonably expected to cause the failure of a critical device, or to affect the device’s safety or effectiveness.

 
Critical Device – A device intended for surgical implantation into the body, or used to support or sustain life. The failure of the device to perform, when properly used in accordance with instructions for use provided in the labeling, can be reasonably expected to result in significant injury to the user.

Critical Instrumentation – Those instruments which are pertinent to the proper operation, control and recording of Critical Process Parameters (i.e., temperature, pressure controllers and/or recorders utilized for the documentation of process release parameters).

 
Critical Operation – Any operation in the manufacture of a Critical Device which, if improperly performed, can be reasonably expected to cause the failure of a Critical Device or to affect its safety or effectiveness. 12
Critical Process Parameter – A control parameter that has a direct relationship to the quality, safety, effectiveness or performance of the intermediate or final product.
 
Critical Process Parameter (CPP) – A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality.
 
Critical Quality Attribute (CQA) – A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

Critical Surface(s) – Surfaces that come in contact with sterilized product or containers/closures (i.e., filling pumps and needles). 

 
Critical System – A system whose performance has a direct and measurable impact on the quality of the intermediate or final product. A system determined to be “critical” must be designated as such, and must be maintained and operated using approved Standard Operating Procedures (SOP).

Cross Contamination – The traces of product from one product to another or from one Batch to another.

Curvilinear – Characterized by curved lines. Some analytical methods, such as particle beam mass spectroscopy (PBMS), are inherently nonlinear. It may be appropriate to use non-linear least squares equations. There must be a scientific basis for these equations, and the acceptance criteria of the other characteristics must be met.
Dangerous Goods – Articles or substances that are capable of posing a significant risk to health, safety or property when transported in commerce. This term is commonly used for international shipments throughout the world.32 (See Hazardous Material.)
 
Dashboard – A collection of quality, compliance, and/or performance measurements which help management measure and control the risks associated with operating within a regulated industry.
 
Data – Any representation of facts, concepts, information or instructions, such as alphabetic or numeric characters, to which meaning can be assigned for communication, interpretation or processing by humans (or LIMS).
Database – A collection of data fundamental to a system.
Deadleg – An area of stagnation in a pipeline, six pipe diameters in length (six times the unused portion of pipe) or greater.
Dedicated Equipment – Equipment that is permanently used for the production of one product only.
Defect – 1] Any non-conformance characteristic with specific requirements. 26 2] A departure of a quality characteristic from its intended level or state that occurs with sufficient severity to prevent an associated product or service satisfying its intended normal, or foreseeable, usage requirements 
Degrees of Freedom (DF) – Generally equal to the number of observations minus the number of constants calculated from it.
Deionization – A purification process that uses synthetic resins to accomplish a selected exchange of H+ and OH– ions for the ionized impurities in the water.
 
Deionized Water (DI Water or DIW) – Water produced by passing treated water through either a mixed-bed or two-bed ionic (cation/anion) exchange resin system. (See Purified Water and Reagent Grade Water.)

Depyrogenation – The elimination of all Pyrogenic substances, including bacterial endotoxin. This is generally achieved by the removal of inactivation. Inactivation can be accomplished during a dry heat sterilization/depyrogenation process with temperatures in excess of 2500C, or by exposure to acid/base hydrolysis, oxidation, ionizing radiation, etc. The FH is usually calculated using a base temperature of 1700C and a Z-value of 540C. A  Z-Value of 200C has been used, but this was derived from sterilization data based on B. subtilis spore bioburden.

Design – (Software Life Cycle)  The stage that specifies the automated and manual functions and procedures, the computer programs and the data storage techniques that meet the requirements and security and control techniques identified to assure the integrity of the system.

 
Design History File (DHF) – A compilation of records that describe the design history of a finished device.

Design History Record – A compilation of records containing the complete design history of a finished device.

Design Input – The physical and performance requirements of a device that are used as a basis for device design.

 
Design Output – The  results of a design effort at each design phase, and the end of the total design effort. The total finished design output consists of the device, its packaging and labeling, the associated specifications and drawings, the production and quality system specifications and the procedures which are included in the Device Master Record (DMR).
 
Design of Experiment (DOE) – A systematic approach to problem solving that applies statistical principles and methods at the data collection stage so as to generate valid data in support of scientific research and development. It is often carried out under controlled conditions to minimize systematic biases or random variations, ensure validity of statistical tests performed on the data, and reduced costs associated with the experimentation.  
Design Qualification – The review of design concepts, at an early stage in a project, for conformance to operational and regulatory expectations.

Design Review (Architectural Review) – 1] A planned, scheduled and documented audit of all pertinent aspects of a design that can affect performance, safety or effectiveness of a piece of equipment, system or facility. 26 2] A comprehensive, systematic examination of a design to evaluate the adequacy of the device requirements to evaluate the capability of the design to meet those requirements and to identify problems with the design and design requirements so solutions can be proposed to all such problems. 12 3] A technique of evaluating a proposed design to ensure that the design: a) Is supported by adequate materials that are available on a timely basis; b) Will perform successfully during use; c) Can be manufactured at low cost; and d) Is suitable for prompt field maintenance.

 
Design Space (DS) – The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.
 
Design Validation – 1] The comparison of the product against the user requirements that were agreed to, at contract review stage, and detailed in the design outputs. 67 2] Establishing by objective evidence that device specifications conform with user needs and intended uses. Further defined in section 820.30(g).

Design Verification – 1] The comparison of design output with design input. 67 2] Confirmation (by examination and provision of objective evidence) that the design output meets the design input requirements.

Device – 1] An instrument that will give analytical answers as a result of electrical or mechanical measurements on an element, compound, solution, instrument, system, etc. 2] “An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article ... which is ... intended for use in the diagnosis of disease or other conditions or in the cure mitigation, treatment, or prevention of disease, in man ... or intended to affect the structure or any function of the body of man ... and which does not achieve its primary purpose through chemical action within or on the body of man ... and which is not dependent upon being metabolized for the achievement of its primary intended purposes.” (Food, Drugs and Cosmetics Act)

Device History Record (DHR) – A compilation of records containing the complete production history of a Finished Device.

Device Master Record (DMR) – 1] A compilation of records containing the design, formulation, specifications, complete manufacturing procedures, quality assurance requirements and labeling of a Finished Device. 12 2] A compilation of records containing the procedures and specifications for a finished device.

Dew Point – 1] A point in the temperature range where the wet-bulb and dry-bulb temperatures are equal. 2] Moisture condenses from the air at a point causing dew, rain, fog or condensation.

 
Diagnostic Specimen – Any human material (including, but not limited to, excreta, secreta, blood and its components, tissues and tissue fluids) being shipped for the purpose of diagnosis.

Digital – Relating to separate, discrete information.

Dioctyl Phthalate (DOP) – Material most commonly used for testing HEPA Filters with a 0.3 µm aerosol. It is a suspected carcinogen. May be replaced by a group of non-carcinogenic poly-alpha olefins (PAO), like Emery 3004 (which is primarily used as a synthetic lubricant), or highly refined vegetable oils.

 
Discrete-Particle Counter (DPC) – An instrument, such as an optical particle counter or a Condensation Nucleus Counter (CNC), capable of resolving responses from individual particles. 

Disinfectant – An antimicrobial agent which destroys pathogenic organisms on inanimate objects. A Germicide that inactivates virtually all recognized forms of pathogenic microorganisms but not necessarily all microbial forms (e.g., bacterial endospores) on inanimate objects. Germicides include Sterilants and Disinfectants, and are registered and regulated by the EPA.

 
Disinfection – A process that eliminates many or all pathogenic microorganisms except bacterial spores on inanimate objects. This is generally accomplished by the use of liquid chemicals or wet pasteurization in health care settings. The efficacy of disinfection is affected by a number of factors, each of which may limit or nullify the efficiency of the process. Some of the factors that have been shown to affect efficacy are the prior cleaning of the object, the organic load on the object, the type and level of microbial contamination (Bioburden), the concentration of and exposure time to the Germicide, the physical configuration of the object (e.g., crevices, hinges, lumens), and the temperature and pH of the Disinfection process. There are several levels of disinfection:
  • High-Level Disinfection – Expected to destroy all microorganisms, with the exception of high numbers of bacterial spores.
  • Intermediate-Level Disinfection – Inactivates Mycobacterium tuberculosis, vegetative bacteria, most viruses and most fungi but does not necessarily kill bacterial spores.
  • Low-Level Disinfection – Can kill most bacteria, some viruses and some fungi but can not be relied on to kill resistant microorganisms such as tubercule bacilli or bacterial spores. 
Dissolving – The direct solubilization, without significant chemical degradation, of residues in water or cleaning solution.

Distillation – A purification process involving phase changes (from liquid to vapor to liquid) leaving behind certain impurities.

Distribution (or Probability of Distribution) – A mathematical function characterized by constants (parameters) that relate the values that a variable can assume to the probability that a particular value will occur. The frequencies with which observations of given magnitudes occur in a sample.

Documentation – Manuals, operating records, specifications, procedures, policies or reports – written or electronic – that provide information describing, defining, specifying, reporting or certifying activities, requirements, procedures or results concerning uses, maintenance or validation of a process or system, which can involve hardware, software or both. This material may be presented from electronic media.

Document Control Number (DCN) – A unique number or distinctive combination of letters or numbers, or both, assigned to a document to control, monitor and retrieve it from a controlled document file system.

Document Supplement – An approved document used to provide supplemental information for an operating record, specification, or procedure. A document supplement is used to add information retrospectively and is used in lieu of revision of the supplemented document.

Dose – The energy absorbed by a material, per unit mass, when it is exposed to ionizing radiation. As defined by the International System of Units, the unit used for measuring is the Gray (Gy). 1 Gy = 1 J/kg.

Dosimeter – A device that measures doses of radiation.

Dust – An air suspension (aerosol), or particles of any solid material, usually with a particle size le

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