VALIDATION DICTIONARY

Validation Dictionary 2nd Edition | IVT

Validation… “…has indeed, in some quarters, assumed the status of a new religion, with its own mystique, its own
ceremonies and its own special incantations, expressed in an arcane language understood only by initiates.” –
J.R. Sharp, 1985

The Validation Dictionary is an attempt to take the perceived esoteric nature away from the science and art of
validation, total quality management systems and regulatory affairs. This document is a living, dynamic work
which should accurately reflect the knowledge and understanding of all who use it. The use of proper terminology
often eliminates confusion in cGMP/regulatory compliance. In some cases, terminology is published within the
guidelines, manuals, compliance programs, master plans and technical papers by the sponsoring body (FDA,
USP/NF, etc.). To assist my co-workers and fellow professionals, I have compiled this lexicon. There are several
special terms I would like to address in advance i.e., qualification, validation and certification. One qualifies
facilities and utilities; one doesn’t validate them. One qualifies and validates equipment, processes and
procedures. The act of qualification is more of an audit, performed to determine if something is built, installed or
operates correctly. To validate, is to test by use of challenges, either under normal production or worst-case
conditions. Certification is a documented statement by an authorized and qualified individual(s) that an
equipment/system validation, revalidation, qualification, requalification or calibration has been performed
appropriately and that the results are acceptable. Certification may also be used to denote the overall acceptance
of a newly validated manufacturing facility.

When a word or phrase is italicized within the text of a definition, it generally indicates that it is a Key Word or Key
Phrase that is further defined within the lexicon. –Tod E. Ransdell

 Acronyms

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.

C
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.
D
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 less than 100
microns (<100µm).

D-Value – The time, at a given temperature, needed to reduce the number of microorganisms by 90%, or one log.
It is expressed in terms of time (minutes or hours) when dealing with heat, and in megarads when ionizing
radiation is involved. The reciprocal of the D-Value (1/D) is referred to as the death rate constant, “K” or “K-value”.

E
E-Beam Sterilization – A machine-based radiation sterilization method. The E-beam is produced
by an electron accelerator, which produces a very powerful, concentrated beam (beam energies of
5-10MeV are typical of most case-format medical product sterilization applications). The operation
of the electron accelerator is similar to that of a television. The electron accelerator beam is
scanned over a product to ensure uniform treatment. Using two-sided E-beam irradiation on
packages, penetration capabilities – with good beam uniformity– can be as high as 80 cm.

Edge of Failure – A control parameter value that, if exceeded, means an adverse effect on the State of Control
and/or fitness of a product for use.

Electrical Power Quality – Sensitive electronic equipment used for sterilization measurement and control
systems requires high quality, well-regulated continuous electrical power in order to operate reliably and safely.
Precautions need to be taken to protect the sterilization system from line power disturbances caused by voltage
fluctuations, line noise, transient impulses, power outage and frequency variations. Although there is no industry
standard to define “acceptable” electrical power, the Guideline on Electrical Power for ADP Installations (FIPS
Pub. 94), published by the National Bureau of Standards (NIST), Sept. 21, 1983, is recommended for sterilization
measurement and control system applications.

Endotoxin – A thermostable component of Viable or Non-Viable Gram–negative bacteria that may

cause a fever when injected or infused. (See Pyrogen.)
Endotoxin Indicator (EI) – A tool, analogous to the BI, which can be used in the Validation and routine control of
Endotoxin reduction processes. Like the BI, the Endotoxin Indicator provides the user with an In vitro biological
test to complement physical measurement used to control the manufacturing process.

Enterprise Resource Planning (ERP) – A computerized system for integrating company-wide data in order to
improve planning activities, provide better control of operations, and enable products to get to market more
quickly.

Entrainment – The capture of part of the surrounding air by the air stream discharged from an
outlet. (Sometimes called secondary air motion.)

Environment – The condition, circumstances, influences and stresses surrounding and affecting the product
during storage, handling, transportation, installation and use.

Environmental Control Parameters – Those measurements and conditions associated with

facilities and equipment utilized in the Manufacturing Process which have the potential for impacting
on the identity, strength, quality and purity of a product. Among the parameters of concern are air
flow rates and patterns, pressure differentials, materials and personnel flow, temperature and
relative humidity, as well as burdens of such foreign substances as Non-Viable and Viable Particles
or Particulates.

Environmental Factors – Those outside influences on an instrument or system that may affect its operation,
including temperature, moisture, electrical interference, electromagnetic flux (EMF), or power supply.

Environmental Isolates – Isolated microorganism samples from the Environmental Monitoring

Program that represent the microflora of an aseptic processing system, terminal sterilization
processes, non-sterile processes, and medical device operations..

Environmental Monitoring Program – A documented program implemented through Standard Operating

Procedures that describes the procedures and methods used for monitoring particulates and microorganisms in
Controlled Environments (air, surface, personnel gear). The program includes sampling sites, frequency of
sampling, and investigative and Corrective Actions that must be followed if Alert or Action Levels are exceeded.
The methodology used for Trend Analysis is also described.

EPA – Environmental Protection Agency.

Equipment – An item which has an individual function and precise physical limits within the structure. An item of
equipment is made up of several components in accordance with a physical configuration.

Equipment Layout – Graphical representation of an system that denotes the relationship between
and among equipment and personnel. This layout is used in the Risk Assessment Analysis to
determine sampling sites and the frequency of sampling based on the potential for microbiological
contamination of the product/container/ closure system. Changes must be assessed by responsible
managers, since unauthorized changes in the layout for equipment or personnel stations could
result in an increase in the potential for contamination of the product/container/closure system.
Error – Any deviation of an observed value from the true value. When expressed as a percentage of the value
measured, it is called Relative Error. Type I Error: If the true Hypothesis is rejected on the basis of a statistical
test. Type II Error: When it is decided that there is no significant difference between two values when a significant
difference exists.

Establish – Define, document and implement.

Etiological Agent – A Viable microorganism or its toxin that can cause human disease. The term is most
commonly used in the U.S. See Infectious Substance.

Evaluation – Activities that provide objective evidence and a level of confidence sufficient to
demonstrate that the software meets the user and software requirements and software design
specifications. This includes verification and validation activities.

Excessive Heat – Any temperature above 40°C (104°F).

Executive Management – The senior employees of a manufacturer who have the authority to establish or make
changes to the manufacturer’s quality policy, quality system requirements, or to a device’s design specifications,
production, distribution, service, maintenance or installation procedures.

F
Fo – The time, in minutes, to produce the equivalent steam sterilization effect at 121.1°C with an
organism that has a z value of 10°C (18°F) (≈250°F). A measure of the lethality of a sterilization
process.
Calculation for accumulated Fo:
Where:
F0 =
FO = Lethality
TO = The average temperature at time t
z = Assume 10°C for steam (Z-value)
t = Time interval
FH – The time, in minutes, to produce the equivalent dry heat sterilization effect at 170?C (338?F).
A measure of the lethality of the sterilization process. The Z-value may equal either 200C or 540C.
The Z-value of 54?C is based on work done by Akers, 92 and also reported in PDA Technical
Report #7, and is relative to the relative heat resistance of endotoxins. The use of a Z-value of 200C
is based on the relative heat resistance of bacterial Spores.
F Test – A variance ratio test used to decide whether two independent estimates of variance can
reasonably be accepted as being two estimates of the variance of a single, normally distributed,
Universe. 70
F Value – A measure of the microbial inactivation capability of a heat sterilization process. The F
Value is calculated by determining the lethal rate per minute at each process temperature using the
Z-value of the microorganism in the particular solution. The lethality term is exponential and is
solved by determining the analog of the exponent. The lethality relationships are exponential
between any two temperatures that are related by a Z-value term derived from logarithmic microbial
inactivation rates. The F Value is calculated using the following equation:
-T)/Z
xO
L = 10(T
Where: L = Lethality (or F-value or FO) TX = Temperature within the item being heated TO =
Temperature at which D value is determined z = May assume 10?C for steam

Face Area – The total plane area of the portion of a grill, coil or other items bounded by a line tangent to the outer
edges of the openings through which air can pass.

Face Velocity – The velocity obtained by dividing the air quantity by the component Face Area.

Facility – The premises and operational unit(s) that are necessary for producing a product or operating a LIMS.

Facultative – Refers to microorganisms that are capable of growing under varying environmental conditions. For
example, facultative anaerobes can grow under both aerobic and anaerobic conditions. See Obligate.

Failure Modes and Effects Analysis (FMEA) – Is an inductive tool used in product and process
development for analysis of failure modes so as to devise more effective testing and control
strategies. It helps identify potential failure modes based on past experience with similar products or
processes and information obtained from various stages of the product and process life-cycle
development.

Fault – 1] A manifestation of an error in software. If encountered, it may cause failure.22 2] A short circuit – either
line-to-line, or line-to-ground.

Fault Tolerance – The built-in capability of a system to provide continued correct execution in the presence of a
limited number of hardware or software faults.

FBiological – A term used to describe the delivered lethality measured in terms of actual kill of microorganisms on or in
a BI challenge system. The FBiological-value is calculated as DT x LR, where DT is the D-value of the BI system at the
reference temperature (T) and LR is the actual logarithmic reduction (log N0 – log NF) of the BI population
achieved during the cycle.

Filter – A porous material that is used to remove particles from a stream of liquid or gas. Filters can be made
from: non-woven fibers of glass, paper (cellulose), or plastic; woven materials; and porous polymeric films. See
Membrane.

Filtered – IVDs or other materials that have been processed through a filter greater than 0.22µm in size to remove
only certain types of organisms, and their production specifications and product labeling state: 1) The final filter
pore size used; 2) The specific viable microorganisms that have and have not been removed from the product by
filtration; and 3) The specific microorganisms whose presence and absence has been confirmed through testing of
the finished product. (See Sterile Filtered.)

Filter Efficiency Test – Is used to determine a HEPA (or ULPA) filter rating. Downstream readings
represent an average over the entire filter surface and require specialized equipment to sample for
a monodispersed aerosol of 0.3µm size particles. Leaks in a filter might not be detected by this type
of test.
Filter Integrity – Characteristics of a filter that ensure the functional performance of a filter used for liquid or gas
in an aseptic processing system.

Filter Integrity Test – Is performed to detect the presence of individual leaks from the filter media, filter frame and
seal. The HEPA (or ULPA) filter unit is challenged with a polydispersed aerosol of 0.1µm to 0.3µm size particles.

Filtration – A purification process in which passage of liquid through a porous substance leaves
behind certain impurities.

Final Report (Technical Report) – A document summarizing the results derived from the execution of a protocol.
The final report shall include a conclusion, which indicates validation success or failure and designates proven
acceptable ranges for all critical process parameters as determined by the execution of the Validation Protocol.

Final SOP – A revised Working SOP which includes detail derived from operating the equipment, including
operator and maintenance input. It is specifically tailored to a particular process and can be completed after the
validation has been performed and the process operational parameters have been established. Final SOPs are
official documents which provide specific instructions to company personnel for one or more of the following
activities: safety issues, calibration, operation, maintenance and cleaning.

Finished Device – Any device, or accessory to any device, that is suitable for use whether or not it
is packaged or labeled for commercial distribution. A Finished Device includes a device that is
intended to be sterile that is not yet sterilized.

Firmware – A program permanently recorded [e.g., in ROM (Read Only Memory)].

Fitments – Those mated device components that protect from a non–sterile environment, those portions of the
device that must be aseptically connected to other sterile devices, drug containers, medical equipment or the
patient.

Flora – The microorganisms found in a given situation (e.g., reservoir flora).

Flow Chart – A graphical representation of the definition, analysis or solution to a problem in which symbols are
used to represent operations, data, flow and equipment.

Flow Diagram – A graphic representation of a system.

F – A term used to describe the delivered lethality calculated based on the physical parameters
Physical

of the cycle. The F -value is the integration of the lethal rate (L) over time. The lethal rate is
Physical

calculated for a reference temperature (Tref) and z-value using the equation: L = 10(T-Tref)/z.

Fraction-Negative Methods – Fraction-negative methods use the starting population of a biological indicator (N0)
and data in the quantal range to create a two-point line from which the DT-value can be determined. The quantal
range is the exposure period over which a set of replicate test units exhibit a dichotomous response – some are
positive for growth and the rest are negative for growth.
Freezer – A place in which the temperature is controlled thermostatically between -200 and -100C
(-40 to +140F).

Functional Testing – A process for verifying that software performs its intended functions.

Fungal Metabolite – Any substance produced during fungal metabolism.

Fungal Propagules – Fungal elements, such as Spores and mycelial fragments, capable of propagation.

Fungus (Fungi) – Any of a major group of saprophytic and parasitic plants that lack chlorophyll, including molds,
rusts, mildew, smuts, mushrooms and yeasts.

G
Gamma Ray (y) – High energy, short wavelength radiation. Extremely penetrating.

Gamma (Ray) Sterilization – Employs isotopes of either Cobalt 60 (60Co) or Cesium 137 (137 Ce) as a source
of ionizing radiation. The natural decay of 60Co expels two gamma photons with respective energies of 1.17 and
1.33 MeV. The gamma photons react with the material being processed in an atomic-level interaction known as
Compton Scattering. Gamma photons strike free electrons within the material being irradiated, and pass part of
their energy to the electrons as kinetic energy. These displaced electrons are known as fast electrons. The
photons, with whatever energy that remains, deflected from their original paths go on to take part in further
interactions. These further interactions result in the production of a large number of fast electrons, many of which
ionize other atoms, and break vital chemical bonds, and initiate the chain of events that is ultimately expressed as
biological damage. 93 Biological Indicators containing Bacillus pumilus are frequently selected to monitor the
sterilization process. The BI Overkill method requires that a demonstrated six logarithmic inactivation of B. pumilus
on, or in, a product be attained with a minimal dose to assure a 12D or a 12 logarithmic reduction in spore
population. This method necessitates that a minimum dose range of approximately 1.8 to 2.6 megarads (Mrad) be
utilized in an Overkill Process.

Germicide – An agent that destroys microorganisms, particularly pathogenic organisms (“germs”). Other agents
designated by words with the suffix –cide (e.g., virucide, fungicide, bactericide, sporicide, tuberculocide) destroy
the microorganism identified by the prefix.

GLP – Good Laboratory Practices. This term is used in conjunction with toxicity and safety studies performed
under 21 CFR 58.

Goodness of Fit Test – General tests for checking the hypothesis that the data are consistent with
a particular model, thus assessing the validity of the model.

Ground Loop – The grounding of a circuit at more than one point.

H
Half-Cycle Qualification – A qualification method that uses fifty-percent of the exposure time to
demonstrate sterilization cycle efficacy. The physical and biological lethality values achieved in the
half-cycle exposure time are doubled to project the lethality that will be achieved by the full cycle.
Hardware – Physical apparatus or equipment that makes up a computer and its related peripheral
devices (e.g., tape drives, disk drives, printers, etc.) or other system. This term is also used to
describe various pieces of equipment in the system.

Hazardous Material – A substance or material in a quantity and form that may pose an unreasonable risk to
health, safety or property when transported in commerce. This term is commonly used for domestic shipments in
the U.S.

Heat Penetration – Heat penetration testing is a temperature measurement that is used to evaluate
the amount of energy that has been transferred to the materials that are to be sterilized within the
load. For measurements of heat penetration, the probes should be placed on or in the load items
being evaluated.
HEPA Filter – High Efficiency Particulate Air Filter. A type of throw-away, extended medium, dry-
type filter in a rigid frame that is designed to have a minimum particle collection efficiency of 99.97%
to 99.999% when removing particles of 0.3 µm or larger (of thermally generated DOP aerosol, and a
maximum clean-filter pressure drop of 1.0 in., water gate, when tested at a rated air-flow capacity.
The HEPA filter is used either in an in-line filter housing or as a terminal air distribution device.
HEPA Filter Efficiency – The particle removal efficiency of the individual unit as tested with
thermally generated DOP aerosol and an aerosol penetrometer per MIL. STD. 282.
Hepatitis – An inflammation of the liver which can be caused by toxins, drugs, excess alcohol,
bacteria or viruses. There are six (6) distinct viruses that are directly associated with Hepatitis, A, B,
C, D, E and G. Other viruses associated with Hepatitis are Cytomegalovirus (CMV) and Epstein
Barr Virus (EBV).
Hepatitis B Virus (HBV) – A double stranded, circular DNA virus that belongs to the family of
viruses called hepadnaviridae. HBV consists of a central core containing core antigen (HBcAg), a
surrounding envelope containing surface protein or surface antigen (HBsAg) and the e antigen
(HBeAg). The intact viral particle, combined with core DNA and DNA polymerase, is called the
“Dane particle”.

High Performance Liquid Chromatography (HPLC) – An analytical technique for performing

chromatographic separations in which the eluent, or carrier, is a liquid under pressure. A liquid
chromatograph usually consists of an injection system, column, high-pressure pump, column oven
or heater, detector, recorder and control module.
Histogram – A graphic presentation of a frequency distribution. It is constructed by erecting bars or
rectangles on the class intervals.
Homogeneity of Variances – If a set of estimates of a variance do not differ more than could be
expected due to chance, they are said to be homogeneous.
Hot Junction – Original name for the Measuring Junction, or sensor, of a Thermocouple.

Human Factors – The understanding of how human capabilities, expectations, and limitations
affect the user’s interaction with the software and hardware capabilities of a software system.
Hypha (pl. Hyphae) – One of the (Vegetative) filaments of a Mycelium.
Hypothesis – An assumption made concerning a parameter to provide a basis for a statistical test.
It is usually expressed as a null hypothesis or as an alternative hypothesis.
I
Immunoassay – The use of antibodies to identify and qualify substances. The binding of antibodies
to antigen, the substance being measured, is often followed by tracers, such as radioisotopes or
phosphors.
Immunochromatography – A chromatographic process in which an antigen or antibody is
adsorbed onto a solid support because of the presence of a specific antibody (antigen) immobilized
on the solid support (e.g., agarose beads, membrane paper). Chromatography implies that the flow
of the solution through the solid support is linear (and normally parallel to the length of the solid
support), and that the affinity adsorbent is attached to a discrete portion or all of the solid support.

Immunoconcentration – A process in which antigen is bound by an antibody immobilized on a

membrane. This is the same as Antigen Capture, but the antigen is captured on a membrane to
facilitate detection and visualization.
Immunoglobulin (IgA, IgE, IgG and IgM) – A class of serum proteins which are rich in antibodies.
Often used, along with more specific monoclonal antibodies, in diagnostic reagents in the health
field.
Industrial Unit – Any group of buildings and equipment making up a complete production line or a
production workshop which is either independent or part of an industrial plant.
Infectious Substance – A substance containing a viable microorganism or its toxin which is known,
or suspected, to cause disease in animals or humans. This term is commonly used throughout the
world.
Information – Any communication or reception of knowledge (e.g., facts, data or opinions) including
numerical, graphic or narrative forms. This can be oral or maintained in any medium, including
computerized databases (floppy or hard disks), papers, microform (microfiche or microfilm), or
magnetic tape.

Inherent Intervention – An intervention that is an integral part of the aseptic process required for
either set-up, routine operation and/or monitoring, e.g., aseptic assembly, container replenishment,
environmental sampling, etc. Inherent interventions are required by batch record, procedure, or
work instruction for the proper conduct of the aseptic process.
Initial Reactive (IR) – Refers to a sample that tests positive the first time it is tested.
Initial Spike – The number of Endotoxin Units added to an Endotoxin Indicator prior to a
depyrogenation process.
Initiation (Software Life Cycle) – A request for the development of a system to meet a need for
information or to solve a problem for the individual making the request.

In-Process Tests – Are tests which may be performed during the manufacture of either the drug
substance or drug product, rather than as part of the formal battery of tests which are conducted
prior to release.
In-Project Risks – A function of risk management. The risk that the project will not deliver
anticipated business benefits within acceptable time and cost constraints.
Inspect – To measure, examine, test or gauge one or more characteristics of an entity and
compare the results with specified requirements in order to establish whether conformance is
achieved for each characteristic. ANSI/ACQC 34–1994.
Inspection – The process of measuring, examining, testing or otherwise comparing a unit of
product with the requirements for it.
Inspection by Attributes – An inspection where a unit of product is classified as conforming or
non-conforming, or the number of nonconformities in the unit of products is counted. This is done
with respect to a given requirement or set of requirements.
Installation and Operation (Software Life Cycle) – Incorporation and continuation of use of a new
system by an organization.

Installation Qualification (IQ) – 1] The performance of documented verification that an

equipment/system installation adheres to approved contract specification and achieves design
criteria. The IQ is developed from P&IDs, electrical drawings, piping drawings, purchase
specifications, purchase orders, instruments lists, engineering specifications, equipment operating
manuals and other necessary documentation. All developmental documentation will be included in
an IQ. The manufacturer’s recommendations, local and state codes and the cGMP should also be
considered. The IQ precedes the Operational Qualification (OQ). 2, 18, 19, 23, 52, 56 2]
Establishing the documentary evidence that a sub-system or equipment is installed in compliance
with the technical specifications, standards, codes and regulations. 24 3] Documented verification
that all key aspects of hardware installation adhere to appropriate codes and approved design
intentions and that the recommendations of the manufacturer have been considered.
Instrument List – A listing of all instruments in a system, including their operating ranges, output
signal, selected manufacturer, proposed calibration frequency, etc. Each instrument in the list is
uniquely identified and can also be found on the P&ID.

Integration Testing – An orderly progression of testing in which software elements, hardware

elements, or both are combined and tested, to evaluate their interactions, until the entire system has
been integrated.
Integrity – Sound, unimpaired or perfect condition. The computer security characteristic that
ensures computer resources operate correctly and data in databases are correct. This characteristic
protects against deliberate or inadvertent unauthorized manipulation of the system and ensures and
maintains the security of entities of a computer system under all conditions. Integrity is concerned
with protecting information from corruption.

Intended Use – Provides a complete picture of the software functionality and its purpose.

Intervention – An aseptic manipulation or activity that occurs within the critical area.
Investigational New Drug (IND) – A new drug, antibiotic drug or biological drug that is used in a
clinical investigation. The term also includes a biological product that is used in vitro for diagnostic
purposes. The term “investigational drug” and “investigational new drug” are synonymous.
In Vitro – Culturing life in a cell free system, without cell walls. This is more normally described as
in artificial environment: in an artificial environment rather than inside a living organism (e.g., in a
test tube)
In Vivo – Culturing life within a cell or organism.

International Oganization for Standardization (ISO) – An organization that standardizes procedures across a
variety of countries. It produces documents that provide international guidance on a variety of topics, e.g.,
requirements for cleanrooms, sterilization, and so forth.

Isoaxial – A condition of sampling in which the direction of airflow into the sampling probe inlet is
the same as that of the unidirectional airflow being sampled.
Isokinetic Sampling – The condition of Isoaxial sampling in which the mean velocity of the air
entering the probe inlet is the same as the unidirectional airflow being sampled.

Isolator, Closed – A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous,
isolation of its interior from the surrounding environment. Any air exchange with the surrounding environment
takes place only through microbially retentive filters.

Isolator, Open – A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous,
isolation of its interior from the surrounding environment. It may transfer air directly to the surrounding
environment through openings (e.g., “mouseholes”) that preclude the ingress of microbial contamination.

J
Sorry, no definitions were found
K
Kaplan-Meier Method (or Product Limit Method) – A method for analyzing survival data. It is
based on the distribution of variable time periods between events (or deaths).
L
Labeling – Information concerning the contents of a package and associated hazards. This is
usually printed on paper and affixed to the surface of a package.
Laboratory Error – Either an analyst’s mistake or the result of malfunctioning laboratory
equipment.
Laboratory Management – The individuals directly responsible and accountable for planning,
implementing and assessing work and the overall operation of a Facility.
Laminar Air-Flow Clean Room – A Clean Room in which the absolute filtered air makes a single
pass through an enclosure in a layered, parallel-flow pattern, absolute filters cover 80% of the
ceiling (vertical flow) or one wall (horizontal flow), and air velocities are uniform. 18, 20 See
Unidirectional Airflow.
Life Cycle – An approach to computer system development that begins with identification of a
user’s requirements and continues through design, integration, qualification, validation, control and
maintenance, ending only when commercial use of the system is discontinued.
Life Table Method – A method for analyzing survival data. This method is based on the proportion
of study subjects surviving to fixed time intervals after treatment or study initiation.
Limit of Detection (LOD) – The lowest concentration of analyte in a sample matrix that is detected,
although not necessarily quantified, under specific (stated experimental) conditions. LOD is a type
of Sensitivity.
Limit of Quantitation (LOQ) – The smallest amount (lowest concentration) of analyte in a sample
matrix that can be quantified with acceptable Accuracy and Precision under specific (stated
experimental) conditions. LOQ is a type of Sensitivity.
Limulus Amebocyte Lysate (LAL) – An aqueous material obtained by rupturing the cellular
components of the blood (amebocytes) of a North American horseshoe crab (Limulus polyphemus).
This material coagulates in the presence of LPS (Lypopolysaccharide). This is a technique for
quantifying pyrogens. See TAL

Linearity – 1] The measure of a test method’s ability to obtain results directly proportional to the
concentration of analyte in a sample. 66 2] The ability to elicit test results that are directly
proportional to the concentration of analyte in samples within a given Range.
Linear Regression Method – A method for determining the best-fit line for a single item through
points representing the paired values of two measurement systems (one representing a dependent
variable and the other representing an independent variable). Under certain conditions, statistical
tests of the slope and intercept can be made, and confidence intervals about the line can be
computed.
Lipopolysaccharide (LPS) [aka - Lypopolysaccharide] – Predominant component of andotoxins
produced by gram negative bacteria. They are the cause of pyrogenic reactions in parenteral
products.
Liquid–in–Glass Thermometers – This type of Thermometer may be used in temperatures
ranging from approximately -1830C to 4000C (-2970F to 7520F). Generally the accuracy of these
thermometers decreases below -560C (-69?F) where organic thermometric fluids are used. It is also
less accurate above 3000C (5720F) where the instability of the bulb glass may require frequent
calibration. Specifications for ASTM liquid-in-glass (e.g., mercury-in-glass) are given in Ref. 56.
Log-Linear Modeling Techniques – Methods for analyzing qualitative data in which a function of
the probability that a particular event will occur is logrithmically transformed to fit a linear model.
Logistic Regression Method – A specialized Log-Linear Modeling Technique in which the
logarithm of the proportion of a group having a particular characteristic, divided by one minus that
proportion, fits into a Multiple Regression linear model.
Lot (or Batch) – A unit of components or finished devices that consists of a single type, model,
class, size, composition and software version that are manufactured under essentially the same
conditions and that are intended to have uniform character and quality within specified limits.
M
Magnahelic Gauge – An instrument used to measure (in inches of water) differential air pressure
between two spaces. (Trade name of Dwyer Instruments.)
Maintenance/enhancement (Software Life Cycle) – The resolution of problems not detected
during testing, which improves the performance of the product and modifies the system to meet
changing requirements. Full-scale enhancements require full Life Cycle analysis.
Manufacturer – Any person who designs, manufacturers, fabricates, assembles or processes a
Finished Device. This includes contract sterilizers, specification developers, repackers, relabelers
and initial distributors of import devices.
Manufacturing Execution System (MES) – A real-time system for coordinating all data relating to
the manufacture of products and applying them directly to shop floor activities.
Manufacturing Material – Any material used to facilitate a manufacturing process (e.g., a cleaning
agent, mold-release agent, lubricating oil, etc.) which is not intended by the manufacturer to be
included in the Finished Device.
Manufacturing Process – Manufacturing operations including, but not limited to, materials
handling, product processing, fabrication and formulation, product filling, packaging, sampling,
testing and inspection support functions.
Manufacturing Resource Planning (MRP) – An automated system for handling information
directly relating to manufacturing. This includes inventories, bills of materials (BOM) and orders from
purchasing.
Manufacturing Resource Planning II (MRPII) – An expanded version of MRP that includes
enhanced capacity for planning and scheduling the use of manufacturing resources.
Marketing Application – An application for a new drug submitted under Section 505(b) of the Act.
A request to provide for certification of an antibiotic submitted under Section 507 of the Act, or a
product license application for a biological product submitted under the Public Health Service Act.
13
Marking – Information about the contents and shipment of a package which is printed on or affixed
to the surface of the package.
Master Cell Bank (MCB) – Derived from a single colony (bacteria, yeast) or a single eukariotic cell.
It is stored cryogenically to assure genetic stability and is composed of sufficient ampules of culture
to provide source material for the Working Cell Bank (WCB).

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
microbiological contamination of product/closure/container systems. Deviation from the prescribed
flow could result in an increase in potential for microbial contamination. Material/personnel flow can
be changed, but the consequences of the changes from a microbiological point of view should be
assessed by responsible managers and must be authorized and documented.
Mean – The arithmetic average of a series of measurements.
Mean Distribution or Standard Distribution – The average of the deviations of individual
measurements from the average of the set without regard to sign. The use of this term is not
recommended as a measurement of Precision.
Measurement Uncertainty – An estimate of the range of values around the measurement value in
which the accepted value is believed to fall. The total uncertainty represents the sum of a
measurement of the Random Error and the estimated bounds of the Systemic Error.An instrument
or measurement with greater measurement uncertainty than another instrument is said to have less
Accuracy, and vice versa.
Measuring Junction – The electrical connection that comprises one end of the connectors in a
thermocouple which is used as the temperature sensor. See Hot Junction.
Media Fills – A method of Prospectively Validating sterile, Aseptic and microbiologically controlled
IVD assembly processes using a sterile growth nutrient medium to simulate product filling
operations. The nutrient medium is manipulated and exposed to the operators, equipment,
containers, closures, surfaces and environmental conditions to closely simulate the same exposure
the product itself will undergo. The media filled containers are then incubated to determine
contamination or whether microbial specifications are met.
Media Growth Promotion – Procedure that references Growth Promotion Under Sterility Tests
<71>, USP, to demonstrate that media used in the microbiological Environmental Monitoring
Program, or in Media Fill runs, are capable of supporting the growth of indicator organisms and of
Environmental Isolates from samples obtained through the monitoring program.
Median – For samples with an odd number of items, the median is the middle item when the items
are arranged in order of magnitude. For samples with an even number of items, the median is the
arithmetic average of the two middle items when they are arranged in order of magnitude. The
median is an estimate of the mean for symmetrical distributions.
Medical Device Vigilance (MDV) – The requirements of the Active Implantable Medical Device
Directive and the Medical Devices Directive for Competent Authorities to record and evaluate
adverse incidents, and for manufacturers or their authorized representatives to report incidents. The
European Commission established a working group to develop a system that could be adopted by
all concerned. The result was a Guideline on Medical Device Vigilance.
Membrane – A porous, thin, polymeric film that is characterized by considerable homogeneity on a
microscopic scale. Unlike non-woven or woven filters, membranes are made up of a continuous
lattice of polymer having no, or few, unconnected fibers or particles. (See Table 3 – Summary of
Membrane Physical Data)

Method Validation – The documented demonstration that a test method is scientifically sound and
serves its intended purpose.
Microbial Challenge – Systems used in cycle development, validation and routine monitoring that
demonstrate the microbial lethality of the sterilization process.

Microbiological Assurance Level (MAL) – A process specification that assures microbiologically

controlled In Vitro Diagnostics (IVDs) are manufactured under appropriate conditions and controls
which will result in a product that consistently meets all its specifications, where the MAL is
commensurate with the need for safe and effective performance of the IVD.
Microbiological Content – The quantity of viable organisms, as determined by total colony count,
after incubation at 36 ±1?C for 24 hours, followed by 24 hours at ambient temperature (23 ± 3?C).
This is reported as colony forming units per milliliter (CFU/ml). This definition is only valid for
conventional methods. Rapid methods typically use organisms, light units or other methods to
describe the content.
Microbiologically Controlled IVD – An In Vitro Diagnostic (IVD) which may contain
microorganisms that have been shown through process validation not to adversely affect, when
stored according to the IVDs labeling, product performance throughout the product’s expected shelf
life.
Microbiologically Uncontrolled IVD – An IVD which contains components that are toxic to
microorganisms (preservatives) or do not support the growth of microorganisms. The remains or
byproducts of any microorganisms in the IVD do not adversely affect product performance.
Microfiltration (MF) – Removes particles in the range of approximately 0.1µm to 1.0µm. In general,
suspended particles and large colloids are rejected while macromolecules and dissolved solids pass
through the MF membrane. Applications include removal of bacteria, flocculated materials, or Total
Suspended Solids (TSS) from cooling water. Transmembrane pressures are typically 10 psi.
Mini-environment – A well defined area that has been isolated from the general environment by
some form of barrier. A type of isolation technology for manufacturing.
Minimum Required Fo – Determination of the lethality required for a new sterilization cycle or load
configuration. 15
Fo = D121(log10A – log10B)
Where: D121 = Time at 1210C to reduce population by 90% B = Probability of Survival A =
Bioburden (or population of BI)
Mode – The most frequent value in a frequent distribution.
Module – A unit task or subdivision.
Monitoring – The routine determination of airborne Particle concentrations, as well as other
relevant conditions, in Clean Rooms and Clean Zones.
Mrad – Expression of radiation dose. See Dosimeter and Rad. 1
Multiple Regression Analysis – A multivariate extension of Linear Regression in which two or
more independent variables are fit into a best linear model of a dependent variable.
Multiproduct Facility – Manufacturing facility containing areas for the processing of two or more
products concurrently or on a Campaigned basis.
Mycelium (pl. Mycelia) – A (vegetative) mass of Hyphae. The (vegetative) body of a fungus.
Mycotoxicosis – Poisoning of animals and humans by feed and food products contaminated with
toxin-producing Fungi.
Mycotoxin – A metabolite produced by Fungus that is toxic to animals and humans.
N
Nanofiltration (NF) – A specialty Membrane process which rejects particles in the approximate size
range of 1nm (1 nanometer or 10 Angstroms). NF operates in the realm between UF and Reverse
Osmosis. Organic molecules with molecular weights greater than 200-400 are rejected. Also,
dissolved salts are rejected in the range of 20-98%. Salts which have monovalent anions (e.g.,
sodium chloride or calcium chloride) have rejections of 20-80%, whereas salts with divalent anions
(e.g., magnesium sulfate) have higher rejections (90-98%). Typical applications include removal of
color and TOC from surface water, removal of hardness or radium from well water, overall reduction
of Total Dissolved Solids (TDS), and specialty food and wastewater applications. Transmembrane
pressures are typically 50 to 225 psi.
NIST – National Institute of Standards and Technology (formerly the National Bureau of
Standards).
Non-Conformance – A product condition in which one or more characteristics do not conform to
requirements. Includes failure, deficiencies, defects and malfunctions.

Non-Condensable Gases – Air and other gases that will not condense to liquid state thereby not releasing latent
heat under the conditions of sterilization.

Non-condensable Gases – Noncondensable gas is gas (e.g.,air, nitrogen and CO2) that may be
carried over in steam from the steam generator. These noncondensable gases change the steam
from pure, vapour-phase water to a mixture of steam and gas.

Non-Conforming – The failure of a component, manufacturing material or finished device to meet

its specifications. This can happen before or after distribution of the finished device.
Non-Conformity – A departure of a quality characteristic from its intended level or state that occurs
with a severity sufficient to cause an associated product or service not to meet a specification
requirement. 35 Non-Critical Device – Any Finished Device other than a Critical Device.
Non-Critical Instrumentation (Reference Instrumentation) – Any instrument that is used
primarily for convenience, operator ease or maintenance. These instruments do not directly control
or monitor process parameters or impact documentation of process control (e.g., use-point gauges).
Non-Dedicated Equipment – Equipment that is used for the production of more than one product.
Non-Parametric Tests – Hypothesis tests that do not require data to be consistent with any
particular theoretical distribution, such as Normal Distribution.
Non-Process-Related Error – Where the process itself is acceptable, but an operator’s mistake,
equipment failure, improper composing process intermediate or reagent changes a product’s
composition in such a way that it produces an out-of-specification test result.
Non-Processed Indicator – An Endotoxin Indicator (or Biological Indicator) that has not undergone
a Depyrogenation (or Sterilization) procedure.

Non-Sterilization Process – Any process that purports to do something other than sterilize. It may
be a method associated with, or even integrated to, one that sterilizes. See Sanitization and
Disinfection.
Non-Unidirectional Airflow – Airflow which does not meet the definition of Unidirectional Airflow,
previously referred to as “turbulent” or “nonlaminar” airflow. 3 (See Conventional Clean Room.)
Non-Viable Particle – A Particle, such as dust, lint, aerosol, or skin cells, that has no viable
microbial cells on it.
Normal (Gaussian) Distribution – A body of data, or Universe, whose values exhibit the frequency
of the Gaussian or bell-shaped curve. It is fully characterized by its Mean and Standard Deviation.

Normal Operating Range (NOR) – The expected range of variability for a process parameter
based on equipment/process capability, generally established via statistical analysis of production
data.
O
Objective Evidence – Information which can be proven to be true based on facts obtained through
observation, measurement, test or other means.
Obligate – Refers to microorganisms that are incapable of growing under more than one
environmental condition. For instance, obligate anaerobic bacteria can only grow in the complete
absence of gaseous oxygen. See Facultative.

Observation – An experimentally obtained value.

Occupational Exposure Limit (OEL) – A health-based airborne concentration limit to which worker
exposure levels should be controlled. OEL are usually expressed as eight-hour time weighted
averages for exposures for 40 hours a week over a working lifetime.

Off-the-Shelf-Software (OTSS) – Software that is available as a stock item, not specially designed
or custom-made for any particular consumer.
Ongoing Evaluation – A term used to describe the dynamic process employed after a system’s
initial validation in order to maintain the validation status of the computer system.
Operating Parameter (Operating Variable) – The Process variables which are measured to
monitor and maintain the normal state of a Process or system. All factors, including Control
Parameters, that may potentially affect the Process State of Control and/or fitness for use of the
final product.
Operating System – A set of programs provided with a computer that function as the interface
between the hardware and the applications program.

Operational Facility – Is a Clean Room in normal operation. All services are functional, operating equipment is
installed and personnel are present. 18 (See As-Built Facility and At-Rest Facility)

Operational Qualification (OQ) – 1] The documented verification that the equipment/system

performs per design criteria over all defined operating ranges. The OQ includes qualification of
operating and maintenance records. The OQ precedes the Performance Qualification (PQ). 2]
Establishing the documentary evidence that a sub-system or set of equipment is capable of
repeated operation within the limits defined in the specifications. 24 3] Documented verification that
a system or sub-system performs as intended throughout representative or anticipated operating
ranges. The term Performance Qualification is sometimes used in the same context.
Optical Density (OD) – The absorbancy of light of a specific wavelength by a solution. Often used
to express the amount of a substance in a solution.

Original Observations – The first occurrence of human-readable Information.

Outlier – 1] A quantity that is found in some sets of data that is so different from the other quantities
in the data set that it appears to belong to a different Population. 69 2] A value in a set of
observations which is so different from the rest that it is considered to be a number of another set or
Population.
Outlier Testing – The statistical process by which analysts test the possibility that an outlier really
does belong to another Population of results and can, therefore, be cast out from the set of data
that is being gathered. One simple and straightforward outlier test is the Dixon Method.
Out-of-Specification Event – When one or more of the requirements included in Standard
Operating Procedures for Controlled Environments are not fulfilled. It may be a temporary or
continuous event.
Overkill Sterilization – A sterilization design approach where minimal information is required about
the product bioburden. A worst-case bioburden assumption is used to determine the delivered
lethality needed to achieve a PNSU of 10-6 on or in the items being sterilized. When using this
approach, the qualification program must demonstrate that both the FBIO and FPHY are greater
than 12 minutes.
P
P-value – Is the probability of obtaining a test statistic at least as extreme as the one that was
actually observed, assuming that the null hypothesis is true. One often "rejects the null hypothesis"
when the p-value is less than a pre-specified significance level, which is often either 0.05 or 0.01.
When the null hypothesis is rejected, the result is said to be statistically significant.

Package – The completed product of a packing operation. It consists of the packaging and its
contents prepared for shipment.
Packaging – Assembly of one or more containers, and any other components, which are necessary
to ensure compliance with minimum packaging requirements of applicable regulations.
Packing – The art and operation by which an article, material, or substance is enveloped in a
wrapping and/or packaging or otherwise secured.
Paired T-Test – A test in which two related samples (e.g., before and after measurements) arise
from a study. The test is then based on the difference between the sample values. The test statistic
is called a Student’s “t”.

Parallelism – Potency of a biological therapeutic is often determined relative to a reference

standard, such as via the ratio of EC50 values. Measurement of relative potency is only meaningful
if the test sample behaves as a dilution or a concentration of the reference standard and exhibits a
parallel relationship to the reference standard. Such similarity is called parallelism.
Parameter – The unknown “true” value of the basic properties defining a Population or Distribution,
such as the Mean and the Variance.
Parametric Test – A hypothesis test that requires data to conform to some well-known theoretical
distribution, such as Normal Distribution.

Parametric Release – A sterility release system based upon effective control, monitoring,
documentation, and batch records review of a validated sterilization process cycle in lieu of release
procedures based upon end-product sterility testing.
Parenteral – Products administrated to patients by routes other than the mouth, such as
intravenous (IV) or intramuscular (IM).
Particle – A very small object, or discrete mass, of solid or liquid composition (or both) generally
between 0.001 and 1000 µm in size.
Particle Concentration – Number of individual particles per unit volume of air.
Particle Size – The apparent maximum linear dimension of a Particle in the plane of observation as
seen with a microscope, or the equivalent diameter of a Particle detected by automatic
instrumentation. The equivalent diameter is the diameter of a reference sphere having known
properties and producing the same response in the sensing instrument as the Particle being
measured.
Particulate Matter – Discrete quantities of solid matter dispersed and suspended in gasses or
liquids.
PDA – Parenteral Drug Association.

Pearson’s Correlation – Measures linear dependence between two sets of measurements. It is

estimated based on sample mean, variance of covariance of the measurements.

Penetration Probe – A probe placed in contact with the load item or inside a container of liquid to measure the
temperature of the load item or liquid.

Peptizing – Refers to the degradation and dispersion of proteinaceous residues. Peptizing typically
involves the cleavage of protein residues into smaller peptide chains which are soluble in aqueous
solutions.
Percent Recovery – The assay value divided by the theoretical value and multiplied by 100.
Performance Qualification (PQ) – 1] Documented verification that equipment, systems or
processes operate the way they are purported to do. This operation must be reliable and
reproducible within a specified, predetermined set of parameters, under normal production
conditions and must be in a State of Control. 2] Establishing documentary evidence that operating
characteristics and product are in conformity with the limits defined in the specifications. Critical
parameters (temperature, pressure, flow rate, humidity, etc.) must be stable over time under both
normal and worst-case conditions.

pH – A negative logarithm of hydrogen ion activity. It is measured electrometrically and is

determined by the electromotive force between a glass electrode and a reference electrode when
immersed in an aqueous solution and compared to that measured for reference buffer solutions.

Physical Qualification – A component of performance qualification that demonstrates that pre-determined

physical requirements including temperature distribution and heat penetration are achieved consistently
throughout the load.

Plenum – An air compartment connected to one or more distributing ducts.

Pooling of Variances – A technique which combines estimates of a Variance to achieve a better
estimate of the Variance. Individual estimates should exhibit homogeneity before they are pooled.
Population (a.k.a. Universe) – Statistical reasoning employs the concept of a sample of
observations drawn at random from a Universe of all possible Observations. When a number of
determinations of the same quantity are made, the values obtained are regarded as a random
sample of all the determinations which might have been made if infinite repetitions of the test were
actually performed. A Universe is generally characterized by one or more parameters, such as its
mean and its standard deviation. A finite sample can give only estimates of these parameters.

Porous/Hard Goods Load (P/HG) – A porous/hard goods load consists of items in which the bioburden is
inactivated through direct contact with saturated steam. Porous/hard goods load items include: filters, stoppers,
tubing (hoses), mops, garments, stoppers, cleaning equipment, or machine change parts.

Post-Project or ‘Residual’ Risk – A function of risk management. Even though a project has been
‘successfully completed’ (i.e., the In-Project Risks have been well managed), one of the outcomes
has been the introduction of a new hazard into the operational environment. The Residual Risk
refers to the size and likelihood of such a hazard.
Potable Water – Water that is safe to drink. It must meet EPA Standard for Drinking Water; 40 CFR
141.14; 141.21. The grade of water that should be supplied for the manufacture of Purified Water or
DIW.
Precision – 1] The degree of agreement among individual test results when a procedure is applied
repeatedly to multiple samplings of a homogeneous sample. The precision of an analytical method
is usually expressed as a standard deviation or relative standard deviation (coefficient of variation).
Precision is a measure of the degree of reproducibility of the analytical method under normal
operating circumstances. 14, 45 (See Accuracy.) 2] The agreement of two or more measurements
that are obtained under identical conditions using the same test method. 66, 70 There are various
types of Precision, such as: 70 (ASTM Committee E–15) Duplicability – The agreement between
duplicate or other multiple determinations performed by the same analyst at essentially the same
time.
Repeatability – The Precision of a method expressed as the agreement attained between
independent determinations performed by a single analyst using the same apparatus and
techniques on more than one day. Reproducibility – The Precision of a method expressed as the
agreement attainable between determinations performed in different laboratories.
Preventive Action – Action to eliminate the cause of a potential non-conformity or other
undesirable potential situation.

Probability – Probability is numerical measure representing the likelihood that a particular outcome
will occur. The probability that a particular event occurs is a number between zero and one
inclusive. For example, if a lot consisting of 100 parts has four nonconforming parts, we would say
the probability that a randomly selected parts will be nonconforming is 0.04 or four percent.

Probability of a Non-Sterile Unit (PNSU) – The number that expresses the probability of occurrence of a non-
sterile unit after exposure to a sterilization process. Within the medical products industry, a design end-point
better than or equal to the probability of one non-sterile unit in a million units is expected, i.e., PNSU≤10-
6. [Synonym: Sterility Assurance Level (SAL)]

Probability of Survival – See Sterility Assurance Level.

Probe – A relatively small molecule which can be used to sense the presence and condition of a
specific protein or nucleic acid by a unique interaction with that macromolecule.
Procedure – 1] An approved document listing a specific set of instructions which, when followed,
will produce a product or result defined by a specification. Procedures are used to define and
control the manufacture of materials as well as the operation and/or maintenance of equipment,
systems or processes. 56 2] Specified way to perform an activity. A written or documented
procedure usually contains the purposes and scope of an activity; what shall be done and by whom;
when, where and how it shall be done; what materials, equipment and documents shall be used;
and how it shall be controlled and recorded.
Process – 1] The controlled system. 60 2] Set of interrelated resources and activities which
transform inputs into outputs.

Process Capability – Is a measurable property of a process to the specification. It compares the

output of an in-control process to the specification limits, by calculating the ratio of the spread
between the process specifications (the specification "width") to the spread of the process values,
as measured by 6 process standard deviation units (the process "width").
Process Control Parameter (Process Variable) – 1] The measurements and conditions
associated with the manufacturing process which have a potential impact on the identity, strength,
quality, and purity of a product. Examples of parameters of concern are process rates of flow,
weights, volumes, temperature and pressure. 50 2] The process operating variables that can be
assigned values to be used as control levels or operating limits.
Process Development – Establishing evidence that all Process Control Parameters and all control
parameter ranges are validated and optimized.
Processed Indicator – An Endotoxin Indicator (or Biological Indicator) that has undergone a
Depyrogenation (or Sterilization) procedure.

Process Related Failure – Resulting from an incorrect step in the process. This can happen even
when the operator, equipment, and process material perform correctly. All lots produced by that
process fall into suspicion
Process Validation (Process Performance Qualification) – Establishing documented evidence
that a process does what it purports to do. Process Validation is defined in the FDA Guideline on
General Principles of Process Validation: “Process Validation is establishing documented evidence
which provides a high degree of assurance that a specific process will consistently produce a
product meeting its predetermined specification and quality attributes.” (See Performance
Qualification [PQ].)
Product – Result of activities or Processes. It may include service, hardware, process materials,
software or a combination of those elements. A product can be tangible (e.g., assemblies or
processed materials) or intangible (e.g., knowledge or concepts), or a combination thereof.
Product Contact Areas – Areas and surfaces in a Controlled Environment that are in direct contact
with products, containers, or closures and the microbiological status of those areas 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.
Production – All activities subsequent to design transfer up to the point of distribution.

Product Specific Approach – A moist heat 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.

Product-Specific Design Approach – A sterilization design approach that is based on the characteristics of the
bioburden, on or in the load, and the heat sensitivity of the product that delivers the lethality needed to achieve a
PNSU of 10-6 on or in the items to be sterilized. [Synonym: Bioburden/Biological Indicator Approach] (PDA TR1)

Programming – (Software Life Cycle) Coding of program modules that implement a design.
Prospective Validation – Establishing documented evidence that a system does what it purports to
do based on a written and approved, preplanned protocol. The validation is performed prior to the
manufacture of clinical or marketable product, and the product is not sold until the equipment,
system and process meet the validation acceptance criteria.
Protocol – 1] The written and approved document of an experimental sequence of tests that, when
executed as prescribed, are intended to produce documented evidence that the equipment or
system does what it is designed or claims to do reproducibly. The protocol will address all elements
of the validation sequence relevant to the assay, process, equipment or system being challenged.
The results of the performance of
the protocol shall be documented in a Validation Final Report. 2] A prospective experimental plan
that, when executed, is intended to produce documented evidence that a system has been
validated.
Protocol Addendum (Protocol Supplement) – A document explaining a change or addition to an
original protocol. It must include the reason for the change or addition, and approvals from
responsible representatives.
Proven Acceptable Range (PAR) – All values of a control parameter that fall between the extreme
worst-case conditions. The PAR is determined during the qualification phase.

Purified Water – Water obtained by distillation, ion-exchange, reverse osmosis or any other
suitable process. It is prepared from water complying with EPA regulations for Potable Water and
contains no added substances. Purified Water meets all criteria specified in the USP XXII and XXIII,
Official Monograph’s of Water also described in Section <1231> “Water for Pharmaceutical
Purposes.”
Pyroburden – The resident level of pyrogens naturally associated with a product or component
prior to, Sterilization or Depyrogenation.
Pyrogen(s) – A substance that causes a febrile response when introduced parenterally into the
body. The most common source of Pyrogens are Gram-negative bacteria (the lipopolysaccharide
portion of their cell wall.)
Q
Qualification – 1] Used to describe the Testing and review of a piece of equipment, system or sub-
system of a process to assure its fitness for use. Qualification deals with components or elements of
a process, while Validation deals with the entire manufacturing process for a product. The
qualification procedure is determined by a written and approved Protocol or Testing defined by the
Validation review committee.18, 56 2] Operation aimed at proving, with regard to either materials,
equipment or personnel, that the required conditions are met and that they actually provide the
expected results. 3] Action of proving that any equipment works correctly and actually leads to the
expected results. The word Validation is sometimes widened to incorporate the concept of
qualification. (See Validation.) Action of proving and documenting that any premises, systems and
equipment are properly installed and/or work correctly and lead to the expected results.
Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone
do not constitute process validation

Quality – The totality of features and characteristics, including safety and performance, that bear on
the ability of a device to satisfy fitness-for-use.
Quality Assurance (QA) – 1] The activity of providing, to all concerned, the evidence needed to
establish confidence that the quality function is being performed adequately. 56 2] All activities
necessary to assure and verify confidence in the quality of a process used to manufacture a
Finished Device. 12 3] Quality System – International Standard, ISO 9004 replacement term for
Quality Assurance. 31 4] All the planned and systematic activities implemented within the Quality
System which can be demonstrated as needed to provide adequate confidence that an entity will
fulfill requirements for Quality.
Quality Assurance Unit – Any person or organization element designed by laboratory
management to monitor the LIMS functions and procedures.
Quality Audit – An established systematic, independent, examination of a manufacturer’s entire
Quality System that is performed at defined intervals and with sufficient frequency to ensure that
both quality system activities and the results of such activities comply with specified quality system
procedures. It is also used to determine that these procedures are implemented efficiently, and that
that they are suitable to achieve quality system objectives. Quality Audit is different from, and in
addition to, the other Quality System activities required.

Quality By Design (QbD) – A systematic approach to development that begins with predefined
objectives and emphasizes product and process understanding and process control, based on
sound science and quality risk management. A more systematic approach to development, which
can include, for example, incorporation of prior knowledge, results of studies using design of
experiments, use of quality risk management, and use of knowledge management throughout the
lifecycle of the product.

Quality Control (QC) – The regulatory process through which industry measures actual quality
performance, compares it with standards and acts on the difference.
Quality Function – The entire collection of activities from which industry achieves fitness for use,
no matter where these activities are performed.
Quality Plan – A document setting out quality practices, resources and sequences relevant to a
particular product, service, contract or project.
Quality Policy – The overall quality intentions and direction of an organization with respect to
quality, as formally expressed by the executive management.

Quality Risk Management – A systematic process for the assessment, control, communication and
review of risks to the quality of the drug (medicinal) product across the product lifecycle.
Quality System – 1] All planned and systematic activities necessary to provide adequate
confidence that a product, process or service will satisfy given quality requirements (International
Standard, ISO 9004). See Quality Assurance. 31 2] The organizational structure, responsibilities,
procedures, specifications, processes and resources for implementing quality management. 12 3]
Organizational structure, procedures, processes and resources needed to implement quality
management.

Quality Target Product Profile (QTPP) – A prospective summary of the quality characteristics of a
drug product, as it relates to quality, safety and efficacy, considering e.g., the route of
administration, dosage form, bioavailability, strength, and stability.
R
Rad – A unit of energy or absorbed dose of ionizing radiation equal to an energy of 100 ergs/gram
of irradiated material.

Random Error – The chance variation encountered in all experimental work despite the closest
possible control of all variables. It is characterized by the random occurrence of both positive and
negative deviations from the mean value of the method. The algebraic average of this will approach
zero in a long series of measurements.
Range – 1] The absolute value of the algebraic difference between the highest and lowest values in
a set of data. 70 2] The interval between the upper and lower levels of analyte that have been
demonstrated to be determined with Precision, Accuracy and Linearity using the methods as
written.
RCS – Reuter Centrifugal Sampler.
Reagent Grade Water – Water purified for general laboratory uses. This is broken down into
various levels of purity as specified by several professional societies [College of American
Pathologists (CAP), National Committee for Clinical Laboratory Standards (NCCLS), American
Society for testing and materials (ASTM) and American Chemical Society (ACS)]. Type I (HPLC
grade, similar to USP WFI), Type II, Type III (Similar to USP Purified Water) and Special Reagent
Water. Incidence of microbiological contamination, stated as “Minimum Growth,” however is not well
defined. No specific recommendations are made for pyrogen testing.57 (See Purified Water and
Deionized Water.)
Recertification – The repetition of a documented qualification procedure after minor alterations,
maintenance or repair. The extent of the requalification is determined by the Validation
Committee.56 (See Requalification.)
Record – Any written or automated document (books, papers, maps, photographs, machine-
readable materials, etc.), including specifications, procedures, protocols, standards, methods,
instructions, plans, files, notes, reviews, analyses, and reports – regardless of physical form or
characteristics – made or received by an agency of the United States Government under federal law
or in connection with the transaction of public business and preserved, or appropriate for
preservation, by that agency or its legitimate successor as evidence of the organization, functions,
policies, decisions, procedures, operations or other activities of the government or because of the
informational value of the data in them.
Recoverable Endotoxin – The number of Endotoxin Units which can be detected in a Non-
Processed Endotoxin Indicator.
Reference Instrumentation – See Non-Critical Instrumentation

Regression Analysis – Consists of statistical techniques for modeling and analyzing the
relationship between one or more dependent variables (effects) and one or more independent
variables (causes). It is an effective tool for analytical method and process development. Many
other statistical analyses such as analysis of variance and analysis of co-variance are variants of
regression analysis.
Reference Junction – The electrical connection joining the thermocouple conductor to a copper
wire or measuring device at the end remote from the Measuring Junction. Usually maintained at
00C.
Relative Error – The horizontal difference between a theoretical response curve and an actual
response curve divided by the sample concentration.

Relative Risk Assessment – An evaluation of the risk of disease in a patient who possesses a
certain characteristic relative to one who does not possess that characteristic. Relative Risk can be
assessed as a property of a clinical test.
Relative Standard Deviation (RSD) – The Sample Standard Deviation divided by the Sample
Mean (the resulting quotient is multiplied by 100 to give a percentage). The relative standard
deviation is also known as 100 times the Coefficient of Variation (CV).

Relative Standard Error – The standard error divided by the mean and expressed as a
percentage. It measures relative precision in a mean estimate (see Standard Error, Coefficient of
Variation and Relative Standard Deviation).

Release Management – Making available for a specific use or purpose a particular version of a
configuration item. This includes deployment logistics.
Repeatability – The Precision of a method performed under the same operating conditions (e.g.,
same operator and equipment) over a short period of time. Also known as intra-assay precision.
Repeatedly Reactive (RR) – Refers to a positive sample (IR) that is retested and remains positive.
64
Repeated Measures Analysis of Variance – An ANOVA that analyzes two or more related
measures of the same variable. 76 Replicate – Multiple analysis of one standard concentration or
one sample.
Reprocessing – All or part of a manufacturing operation which is intended to correct non-
conformance in a component or finished device.
Reproducibility – The measure of a test method’s variability with different analysts, laboratories or
other conditions. 66 (See Ruggedness.)
Requalification – The approved written procedure used to return a process, piece of equipment or
system to a validated or qualified state after maintenance or minor changes have been made to it.
Especially applicable to those systems used to control or measure critical parameters. The
Validation Committee determines the extent of the requalification required, depending on the repair
or maintenance procedures performed.
Residual Endotoxin – The number of endotoxin units which can be detected in a Processed
Endotoxin Indicator.
Resistance Temperature Detector (RTD) – A temperature measuring device containing a resistor
whose value changes with temperature in a known manner.

Resistometer – Test equipment designed to create defined combinations of the physical and / or chemical
variables of a sterilization process. Resistometers were formally called biological indicator evaluator resistometers
(BIER) vessels. The resistometer is used primarily in the laboratory to determine D and z-values.

Respirable Particles – Those particles that penetrate and are deposited in the non-ciliated portion
of the lung. Particles greater than 10 µm aerodynamic diameter are not respirable.
Restricted Article – A substance, material or article that is subject to the regulations governing the
shipment of hazardous materials or dangerous goods.
Retentive Filters – A filter placed in the process or product line to trap contaminants, where filter
porosity may vary depending on the type of contaminant’s being retained
Retrospective Validation – Establishing documented evidence that a system does what it purports
to do based on a review and analysis of historical data and information obtained during the
production of clinical or marketable product.
Revalidation – The repetition of the Validation sequence, or a specific portion of it, to assure that
the system is suitable for use after modification, repair or maintenance that could alter the product
characteristics or performance. Revalidation is also required periodically (e.g. annually) on critical
processes (Sterilization, Depyrogenation, etc.) even if modifications or repairs are not made. This is
done to insure that the process or system is not undergoing some subtle undetectable changes or
degradation.

Reverse Osmosis Water (RO) – Water produced by a process which uses a membrane under
pressure to separate a relatively pure solution (or other solvent) from a less pure solution.
Resistance Thermometers – The standard platinum resistance thermometer (Platinum RTD) is the
most accurate standard for use with temperatures ranging from approximately -253?C (-423?F) to
630.5? C (1167? F). In cases where an uncertainty approaching 0.1?C is necessary at
temperatures below -56? C (-69? F) or above 200?C (392? F) there are few alternatives to the use
of resistance thermometers as standards.
Risk Assessment Analysis – Analysis after the identification of contamination potentials in
Controlled Environments to establish priorities in terms of severity and frequency. Used to develop
methods and procedures that will eliminate, reduce, minimize or mitigate their potential for microbial
contamination of the product/container/closure system.

Risk Management – Systematic application of management policies, procedures, and practices to

the tasks of analyzing, evaluating, controlling, and monitoring risk.
Robustness – The capacity to remain unaffected by small, but deliberate variations in method
parameters and provide an indication of its reliability.
Room Temperature – The temperature prevailing in a working area. (See Controlled Room
Temperature.)
Ruggedness – The degree of Reproducibility of test results obtained by the analysis of the same
samples under a variety of normal test conditions (e.g., different laboratories, different analysts,
different instruments, different lots of reagents, different elapsed assay times, different assay
temperatures, different days, etc.). Ruggedness is normally expressed as the lack of influence of
operational and environmental variables of the analytical method on test results. Ruggedness is a
measure of reproducibility of test results under normal expected operational conditions from
laboratory to laboratory and from operator to operator.
S
Sample – Consists of one or more units of product drawn from a lot or batch. Units of the sample
are selected at random without regard to their quality.
Sample Mean (x) – The sum of the sample values (?s) divided by the number of samples (n).
Sample Size – The number of units of product (or items of interest) in a sample (n).
Sample Standard Deviation(s) – The positive square root of the population variance. The root-
mean-square average deviation of an observation from the mean.
Sampling Plan – A documented plan that describes the procedures and methods for sampling of a
Controlled Environment. It identifies the Sample Sites, the frequency and number of samples, the
analysis of data and the interpretation of results.
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.
Sanitization – 1] Chemical and physical process used to kill bacteria or reduce contamination. 2]
The act of reducing the number of microbial contaminants to a safe or relatively safe level. Can be
expressed as having a Sterility Assurance Level of ?10–3. Less effective than sterilization (SAL
?10–6). (See Non-Sterilization Process.)
Saponifying – This process specifically involves the chemical degradation of lipids, which are not
freely soluble in aqueous solutions, and is most often accomplished by a hydration reaction.
Secondary Air – The air surrounding an outlet that is captured or entrained by the initial outlet
discharge airstream (furnished by a supply duct or fan).
Secondary Service – Voltage Service up to 600 volts.
Selectivity (a.k.a. Specificity) – The ability to measure accurately and specifically an analyte in the
presence of components that may be expected to be present in the sample matrix. Selectivity may
often be expressed as the degree of bias of test results obtained by analysis of samples containing
added impurities, degradation products, related chemical compounds or placebo ingredients when
compared to test results from samples without added substances. The bias is expressed as the
difference in assay results between two groups of samples.
Sensing Device – A device that keeps track of measurement conditions and their fluctuations so
that when sufficient variation occurs it will originate a signal to revise the operation of the system
and offset the change. Example: A thermostat “bulb”. A Sensing Device may be an integral part of a
controller.
Sensing Element – The first system element or group of elements. The Sensing Element performs
the initial measurement operation.
Sensitivity – The ability to detect low levels of antigen or antibodies with an assay.
Sensor – A Sensing Element.
Servicing – Maintenance or repair of a finished device for purposes of returning a device to its
Specifications.
Set-Point – The value of a controlled condition at which the instrument is set to operate.
Shelf Life – The shelf life of a drug product is the time period during which the average
characteristics such as identity, potency and purity of the drug product remain within their respective
specifications.
Software – A collection of programs, routines, and subroutines that control the operation of a
computer or computerized system.

Source Code – An original computer program expressed in human-readable form (program

language), which must be translated into machine-readable form before it can be executed by the
computer.
Source Program – A program in source language, that must be translated into an object program
before being executed by a computer. A source language is not readable by a computer.
Special Process – Any process whose results cannot be completely verified by subsequent
inspection and testing.
Specification(s) – 1] An approved quantitative value. Specifications are used to define raw
materials, in-process materials, products, equipment and systems. A specification may be
accompanied by a statement as to how it was derived. 56 2] The documents that prescribe the
requirements which a device, component, production or servicing activity, or quality system must
conform.
Specification(s) Qualification (SQ) – The performance of a documented evaluation of the
Specification for a piece of equipment or system to assure that it will adequately perform the
intended function and in a condition fit for use. The conclusion section of the final report shall clearly
state whether the specification is acceptable or not. 55, 56 (See Commissioning [Pre–IQ].)
Specificity – 1] The ability to call a true negative a negative. 64 2] The ability of a test method to
measure an analyte without interference from other sample or matrix components (e.g., synthesis
precursors, excipients, known impurities, and degradation products). (See Selectivity.)
Specific Resistance or Resistivity – The electrical resistance, in ohms, measured between
opposite faces of a 1 cm cube of an aqueous solution at a specific temperature. For these
specifications (NCCLS) the resistivity will be corrected to 25?C and reported in megaohm-cm.
Sponsor – A person who takes responsibility for and initiates a clinical investigation. The sponsor
may be an individual or a pharmaceutical company, government agency, academic institution,
private organization or other organization. The sponsor does not actually conduct an investigation
unless the sponsor is a Sponsor-Investigator.
Sponsor-Investigator – An individual who both initiates and conducts an investigation, and under
whose immediate direction the investigational drug is administered or dispensed.
Spore – A general term for a reproductive structure in Fungi, bacteria and cryptogams. It is a
dormant form of a microorganism that confers resistance to adverse environments. In Fungi, the
term is used in several combinations (e.g., chlamydospore, ascospore, basidiospore and zoospore).
In the context of Sterilization, this is when they are most resistant to destruction by the Sterilization
method.
Spore Log Reduction (SLR) – An expression of the amount of kill of the Microbial Challenge. A
one SLR refers to a one-logarithm decrease or a 1D (90%) reduction of the initial bacterial (or
Fungal) Spore population.

Stability Testing – Is a study which includes design of experiment and analysis of data, and which
is designed to provide evidence on how the quality of a drug substance or drug product varies with
time under the influence of a variety of environmental factors such as temperature, humidity, and
light, and to establish a re-test period for the drug substance or a shelf life for the drug product and
recommended storage conditions.
Standard Deviation (SD) – A measure of the dispersion of a series of results around their average,
expressed as the square root of the Variance.

Standard Error (SE) – The standard error (SE) of the mean of the averages (M) is determined by
dividing the standard deviation (SD) by the square root of the number of locations “L”. SE = SD/ ?L
Standard Operating Procedures (SOP) – Written procedures describing operations, Testing,
sampling, interpretation of results and Corrective Actions that relate to the operations that are taking
place in a Controlled Environment and auxiliary environments. Deviations from the SOPs should be
noted and approved by responsible managers.
State of Control – A condition in which all operating and control parameters for a process or
system that can affect performance are maintained within specified acceptable limits so a system or
process performs consistently and as intended.
Statistic – An estimate of a Parameter.
Steam-in-Place (SIP) – The process for steam sterilizing (or sanitizing) process systems (tanks,
vessels, lyophilizers, filling machines, distribution lines, etc.) without dismantling and autoclaving.
Sterile (Sterility) – 1] The state of being free from viable microorganisms. 18 Products meeting the
criteria of Terminal Sterilization are verified as Sterile. 45 2] The complete absence of viable
microorganisms from a product, as defined in USP, Section <1211>.
Sterile Field – In aseptic processing or in other Controlled Environments, it is the space at a level
with, or above, open product containers, closures or product itself, where the potential for microbial
contamination is highest.
Sterility Assurance Level (SAL) – 1] The likelihood of something that has undergone a sterilization
procedure being non-sterile (expressed as 1 x 10–x . A.k.a. “Probability of Survival” ).
The formula for calculating the SAL is:
log10B = log10 A – Fo/D121
Where: B = Probability of Survival A = Bioburden or product D121 = Time at 1210C to reduce the
population of the most resistant organism found in the environment by 90%
Fo = Equivalent minutes at 1210C
2] The probability of an item being non-sterile, dependent on the product bioburden and the lethality
of the sterilization process.

Sterile Filtered (Sterilized by Filtration) – IVDs or other products which have been filtered through
a not greater than 0.22µm filter (which has been suitably challenged as per USP) either to remove
all viable microorganisms, or to remove only certain types of microorganisms, and their production
specifications and product labeling state: A) the final filter pore size used; B) the specific viable
microorganisms that have been removed from the product by filtration; and, C) the specific
microorganisms whose absence has been confirmed through testing of the finished (product) IVD.

Sterility Failure – Following exposure to a sterilization process that has been proven effective,
reproducible and reliable, a BI exhibited growth when incubated. A sterility failure investigation
should be as elaborate and efficient as possible to uncover the cause of the growth, and sterilization
cycles should factor a sufficient overkill capability into the production parameters to compensate for
elements that might interfere with the efficacy of the process.
Sterilization – 1] The process of achieving sterility. 18 2] The process by which chemical and/or
physical conditions are severe enough to assure that a high number of sterilant-resistant
microorganisms will be killed, or from which the Probability of Survival (Sterility Assurance Level) of
any microorganism is less than 10–6 [i.e., one chance in a million that a microorganism will be
viable (SAL ? 10–6)]. Sterilization is intended to convey an absolute meaning, not a relative one.

Stochastic Process Control (SPC) – A statistical method used to monitor and control a process so
as to ensure that it operates in the way as expected. It is aimed at early detection and prevention of
problems, rather than the correction of problems after they have occurred.
Subject – A human who participates in an investigation, either as a recipient of an investigational
new drug or as a control. A subject may be healthy or a patient with a disease.
Sub-System – A division of a System. A sub-system is a functional assembly made up of one or
more items of equipment.

Survivor Curve – Graphical representation of the inactivation of a population of microorganisms with increasing
exposure to a microbicidal agent under stated conditions.

Swabs – Devices that are used to sample irregular or regular surfaces for determination of
microbial (or chemical/physical) status.
System – A set of organized interactive elements perceived or conceived as a clearly identified
whole. It is delimited relative to its environment and it is often possible to define its function.
Systematic Error – A contribution to the total uncertainty compromising the combined effects of all
non-random error sources, known or unknown, which tend to uniformly or predictably offset all
results of repeated applications of the same measurement process at the time of the measurement.
System Suitability – The evaluation of the components of an analytical system to show that the
performance of a system meets the standards required by a method.

System Suitability Evaluations – Physical evaluations (e.g., chamber integrity or air removal) conducted on a
scheduled frequency to demonstrate ongoing control of the sterilizer system.

T
Tachypleus Amebocyte Lysate (TAL) – An aqueous material obtained by rupturing the cellular
components of the blood (amebocytes) of an Asian horseshoe crab (Tachypleus tridentalus). This
material coagulates in the presence of LPS (Lypopolysaccharide). A technique used primarily in
Japan for quantifying pyrogens. Recently introduced and licensed in the U.S. by the Seikagaku
Corporation. 78 (See LAL)
Tailing Factor (T) – A measure of peak asymmetry as used in chromatographic methods. For a
symmetric peak, the tailing factor is one As the tailing factor increases, the peak becomes more
asymmetric, integration is less reliable and Precision suffers. T = W/2f Where: W = Width of peak at
5% height or width of peak at 5–10% height. f = Distance from the front edge of the peak to the
perpendicular of the peak maximum.

Target Product Profile (TPP) – A format for a summary of a drug development program described
in terms of labeling concepts, to facilitate communication regarding a particular drug development
program.

Technical Report – See Final Report.

Temperature Distribution Study – A study to determine the temperature profile of a sterilizing
medium in a vessel during a sterilization cycle.

Terminal Sterilization – 1] A process where a drug product is sterilized (or resterilized) in its final
container. 50 2] A process that reduces the solution presterilization bioburden to a level of 100 CFU,
with a minimum safety factor of an additional six logarithms microbial reduction (i.e., 10–6)

Test Case (Test Script) – A specific set of test data and associated procedures developed for a
specific objective. Some examples are: To exercise a specific program path, or to verify compliance
with a specific requirement. See Protocol.

Test Failure – Occurs when the actual result does not meet the expected result.

Testing – The determination, by technical or scientific means, of the properties or elements of a

product or its components. This includes functional operation and involves the application of
established scientific principles and procedures.

Thermally Generated DOP – An aerosol generated by quenching (condensing) vapor that has
been evaporated from liquid DOP by heat. The aerosol mean particle diameter is between 0.2 and
0.4 µm, with a geometric standard deviation of 1.3.

Thermistor – 1] A solid-state, resistive temperature measuring device. 18 2] A semi-conductor

which exhibits a large, non-linear change of resistance with temperature, used as a temperature
sensor.

Thermocouple – 1] An electrical circuit comprised of two dissimilar materials. A voltage is

generated that is dependent on the temperatures of the junctions forming the limits of the dissimilar
materials. The Reference Junction at one end of the connectors is usually maintained at a constant
temperature or at 00C to allow the Measuring Junction to be used as a temperature sensor. 36 2] A
temperature measuring device constructed by joining two wires of different composition. 18 Type T
thermocouple wire is made of copper and Constantan wires.Type J thermocouple wire is made of
iron and Constantan wires.

Thermometer – An instrument for measuring temperature, especially one having a graduated glass
tube with a bulb containing a liquid (typically mercury) that expands and rises in the tube as
temperature increases. The column above the liquid is filled with nitrogen. Thermometers may be
standardized for total immersion or partial immersion. See Resistance Thermometers and Liquid-in-
Glass Thermometers. 14:<21>, 28
Thermometry – The technology of temperature measurement.
Tolerance – The difference between upper and lower limits, or the range, of a measured variable.
Top-Down – Pertaining to an approach that starts with the highest level of software components in
a hierarchy and proceeds through progressively lower levels to the lowest level component.
Total Bacteria – All viable Aerobic and facultative Anaerobic heterotrophic bacteria in water.
Transfer Area – Any area of a manufacturing plant, other than the weighing, mixing or filling areas,
where components, in-process materials, products and product contact surfaces of equipment,
containers and closures (after final rinse of such surfaces) are exposed to the environment.
Trend Analysis – Periodic review and analysis of Environmental Monitoring Program results that
can be related to time, shift, facility, etc. for patterns that may suggest underlying or developing
problems. Trend Analysis is used to facilitate decision making for requalification of a Controlled
Environment or for maintenance and Sanitization schedules. Trend Analysis may also suggest that
current Alert and Action Limits/Levels do not reflect actual conditions and may indicate that these
limits or monitoring frequencies should be appropriately modified.
t-Test (Student’s t-Test) – The ratio of a normally distributed variate with a zero mean to its
estimated Standard Deviation. This test is used to determine whether the Mean of a set of values is
consistent with their having been drawn from a Population having some specific Mean, or whether
the Means of two sets of values are consistent with the two sets having been drawn from a single
population. A hypothesis test based on the theoretical Student’s “t” Distribution.
U
U Descriptor – The maximum allowable concentration (particles per cubic meter of air) of Ultrafine
Particles. The U Descriptor serves as an Upper Confidence Limit or as the upper limit for location
averages, or both, as appropriate. U descriptors are independent of airborne particulate cleanliness
classes, and may be specified alone or in conjunction with one or more airborne particulate
cleanliness classes.
ULPA Filter – Ultra Low Penetration Air Filter. A type of filter designed to have a minimum
efficiency of 99.999% when removing particles of 0.3 m or larger to 99.99999% on 0.1m particles.
Ultrafiltration (UF) – A process in which water under pressure is forced through a semipermeable
membrane leaving behind a percentage of dissolved organic and suspended impurities, based on
molecular weight and size between 1,000 and 100,000. Provides macro-molecular separations for
particles in the 20 to 1000 Angstrom range (up to 0.1µm). Transmembrane pressures are typically
10 to 100 psi.
Ultrafine Particles – Particles in a size range from approximately 0.02 µm to the upper limit of
detectability of the DPC.
Ultraviolet (Photochemical) Oxidation – A process by which an ultraviolet light source is used to
convert carbon to carbon dioxide.
Unidirectional Airflow – Airflow having generally parallel streamlines operating in a single direction
with uniform velocity over its cross-section. Previously referred to as “laminar” airflow. (See
Laminar Airflow Clean Room.)
Unit of Product – The unit inspected in order to determine its classification as conforming or non-
conforming or to count the number of non-conformities. It may be a single article, pair, set, length,
area, operation, volume or component of an end product or the end product itself. The Unit of
Product may or may not be the same as the unit of purchase, supply, production or shipment.
Universe – A.k.a. Population.

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 Confidence Limit (UCL) – The upper limit of the estimated mean which has been calculated
so that, in a specified percentage of cases, its value exceeds the true population mean when both
means have been sampled from a normal (Gaussian) distribution. In FS209E, a 95% UCL is used.
The 95% UCL of the mean of the averages (M) is determined by adding to the mean the product of
the appropriate UCL factor and the Standard Error (SE). [i.e., UCL = M + (UCL factor x SE)]. See
FS 209E for table of UCL Factors.
V
Validated State – Determination of the correctness of the software with respect to the user needs
and intended uses.

Validation – 1] The overall term for the establishing of documented evidence through defined tests
and challenges, that a system, manufacturing process, analytical method and/or piece of equipment
meets design criteria and that adequate provisions have been established to keep it in a State of
Control so it will produce a product that meets predetermined specifications and quality attributes.
Validation can be conducted either prospectively, concurrently or retrospectively. Validation
activities provide the logical argument and evidence for deployment of a system, piece of equipment
or process. Process Validation is fundamentally Good
Business Practice. Performance characteristics can be expressed in terms of analytical parameters.
Typical parameters that could be considered include Accuracy, Precision, Limit of Detection, Limit of
Quantitation, Selectivity, Range, Linearity, Robustness and Ruggedness. 2] Confirmation by
inspection or Testing, and establishment of documentary evidence that special requirements for a
specific use are met. 3] Action of proving, in accordance with the principles of Good Manufacturing
Practice, that any procedure, process, equipment, material, activity or system actually leads to the
expected results. See Qualification 34 4] The action of proving that any material, process, activity,
equipment or mechanism used in manufacture or control, can, will and does achieve the desired or
intended result. 33 5] A defined program in combination with routine production methods and quality
control techniques which provides documented assurance that a system is performing as intended,
and/or that a product conforms to its predetermined specifications. When practiced in a Life Cycle
model it incorporates design, development, evaluation, operational and maintenance considerations
to provide both operational benefits and regulatory compliance. 48 6] Establishing and documenting
evidence that provides a high degree of assurance a process will consistently produce a result or
product meeting its predetermined specifications. 7] Confirmation by examination and provision of
Objective Evidence the particular requirements for a specific intended use are fulfilled. The
collection and evaluation of data, beginning at the process development stage and continuing
through the production phase, which ensure that the manufacturing processes including equipment,
buildings, personnel and materials are capable of achieving the intended results on a consistent
and continuous basis. Validation is the establishment of documented evidence that a system does
what it is supposed to do.

Validation Capability/Maturity Model – A model (borrowed from Carnegie–Mellon) used to

describe the level of knowledge of Validation. There are four levels to the model: Level 1 –
Validation Unaware: No knowledge of the Theory of Validation Level 2 – Validation Aware: Basic
knowledge of the Theory of Validation Level 3 – Validation Active: Forced to participate by
regulation or customer demand. Level 4 – Validation Enthusiast: Experienced in practice,
recognizing the benefits and limitations and encouraging others to participate.
Validation Change Control – A formal monitoring procedure during which qualified members of a
Validation Committee (and/or others from appropriate disciplines) review the affect of proposed or
actual changes on the manufacturing process to determine the impact on the Validation status.
These representatives may initiate corrective action to ensure the system or process retains, or is
returned to, a validated condition or State of Control. Also see Change Control.
Validation Committee – A cross-functional group of qualified individuals representing each major
division in a company [manufacturing, engineering, development, engineering services, facilities
(including S&EH), production, quality services, R&D, and QA/regulatory affairs or their designates]
that is assembled to review, evaluate and approve all Validation and/or Qualification functions
and/or activities.
Validation Final Report – See Final Report, Technical Report.
Validation Master Plan – The establishment of a dynamic written plan that defines the overall
approach to a Validation project. It will define the terminology to be used in all subsequent
documentation, outline descriptions of the facility site, the manufacturing processes and the scope
and implementation of the Validation Sequence. This document is prepared concurrently with the
construction phase of a project after all equipment and materials have been specified.
Validation Plan – The collection of activities that include, and are specifically related to, computer
system validation itself.

Validation Protocol – See Protocol

Validation Sequence – The specific set of steps undertaken to validate a system, equipment or
process. The Validation Sequence may contain any one (or more) of the following steps, depending
on the size, complexity, function and criticality of the equipment or system. A subsequent step in the
Validation Sequence should not be initiated prior to the completion of a prior step. No step can be
implemented prior to securing an Approved Document (protocol) directing the method of the
execution of the document.

Variance – A measure of the dispersion of a series of results around their average. It is the sum of
the squares of individual deviations from the average of the results, divided by the number of the
results minus one.

Variance Component Analysis – The Variance Components procedure, for mixed-effects models,
estimates the contribution of each random effect to the variance of the dependent variable. This
procedure is particularly useful in estimating intermediate precision in support of analytical method
quantification, validation and transfer.
Vegetative – The physiological state of microorganisms where they are capable of growth and
reproduction. In the context of Sterilization, when they are the most susceptible to destruction by a
Sterilization method.
Verification (Verify) – 1] Comparison of a measurement standard of known accuracy with another
standard or instrument to detect, correlate, or report (but not eliminate) any variation in accuracy of
the item being compared. Verification implies that no adjustment of the compared instrument is
possible or desired to re-establish accuracy. Confirmation, by examination and provision of
objective evidence, that specified requirements related to a product or process have been met.
Confirming and documenting, with valid, objective evidence, that specific requirements have been
met. Verification includes the process of examining the results of an activity to determine conformity
with the stated specifications for that activity and ensuring that a device is adequate for its intended
use. Confirmation by examination and provision of Objective Evidence that specified requirements
have been fulfilled. The application of methods, procedures, tests and other evaluations, in addition
to monitoring, to determine compliance with the quality risk management activities.
Verification Approach – The Verification Approach (to the cleaning process) is the process of
sampling and Testing to ensure that a piece of equipment has been properly cleaned following each
use.
Viable – Capable of life.

Viable Particle – A particle, such as dust, lint, aerosol or skin cells, that has one or more viable
microbial cells on it.
Virus Passage – Each time a virus containing supernatant is added to uninfected cells, or when a
population doubles in size.
W
Warm – Any temperature between 300 C and 400 C (860 - 1040F).
Water for Injection (WFI) –Water purified by distillation or by reverse osmosis (double pass) that
contains no added substance. WFI must also meet criteria specified in USP 23 Official Monograph
of Water.
Wetting – A process that involves the lowering of the surface tension of a cleaning solution, thus
allowing it to better penetrate and degrade surface residues.
Working Cell Bank (WCB) – A quantity of cells derived from one or more ampules of a MCB,
stored cryogenically and used to initiate a production batch.
Working SOP – An SOP written primarily by referencing manufacturers’ manuals and preliminary
design information. It is not generally tailored to a particular process or specific needs. In some
cases, it may only be an outline of data that must be obtained in order to arrive at a Final SOP.
Work Station – An open or enclosed work surface with direct filtered air supply.
Work Zone – A volume within a Cleanroom that is designated for clean work. This volume shall be
identified by an entrance and an exit plane normal to the airflow (where there is laminar airflow).
Worst-Case – A set of conditions encompassing the upper and lower processing limits and
circumstances (including those within the Standard Operating Procedures) which pose the greatest
chance of process or product failure when compared to ideal conditions. Such conditions do not
necessarily induce product or process failure.
X
Sorry, no definitions were found
Y
Sorry, no definitions were found
Z
Z-Value – The temperature change required to cause a one-logarithm (change) decrease in the D-
Value and its expression is in degrees Celsius (?C)

Commonly Used Symbols and Abbreviations

The following is a list of abbreviations that may be used when filling out and completing
specifications of a Qualification (IQ, OQ or PQ) Protocol.
Acronyms
Commonly Used Acronyms
Including selected meanings, definitions and other pertinent information 510(k) – New Device
Application: Premarket Notification Process from

ADE – Acceptable Daily Exposure

ADI – Acceptable Daily Intake
AFITEP – French (European) regulatory group.
AFM – Atomic Force Microscopy: Uses a silicon nitride tip that is held in contact with a surface
being analyzed while the sample is moved to create a raster pattern. Deflections produced in the tip
when surface features are encountered are deflected by a laser-andphotodetector system.
AFNOR – Association Française de Normalisation.
Ag – Antigen(s).
AGVS – Automated Guided Vehicle System.
Acronyms
AHCPR – Agency for Health Care Policy and Research (sister to FDA in the Public Health Service).
AIAA – American Institute of Aeronautics and Astronautics. AIChE – American Institute of Chemical
Engineers. AIDS – Acquired Immune Deficiency Syndrome. AIR – Antigen-specific Immune
Response ALARP – As Low As Reasonably Practicable (Medium, Class II & Class
APA – Aseptic Processing Area
API – Active Pharmaceutical Ingredient
APICS – American Production and Inventory Control Society, Inc. 53
APIMS – Atmospheric Pressure Ionization Mass Spectrometer: Used to measure moisture,
oxygen and total hydrocarbon emissions from ultraclean valve assemblies.
APS – A synonym for media fills. it is a means for establishing the capability of an aseptic process
as performed using a growth medium.
AQL – Acceptable Quality Level: The FDA acknowledges that there are no absolute rules for
selecting a value for the AQL, but states that it is typically based on the nature of product and the
rate of defects that can be tolerated both by the user and the manufacturer for the specific indicated
uses of the IVD. The sampling plan usually accepts that percent defective with a 95% chance of
acceptance.
ARC – AIDS Related Complex.
ARS – Agricultural Research Service.
ARV – AIDS Related Virus or AIDS-Associated Retrovirus.
ASAP – Americans for a Sound AIDS/HIV Policy.
ASCB – The American Society for Cell Biology.
ASCII – American Standard Code for Information Interchange: A standard seven-bit character
code used by computer manufacturers to represent 128 characters for information interchange
among data processing systems, communications systems and other information systems
equipment. An eighth bit is added as a parity bit to check a string of ASCII characters for correct
transmission. 53
ASHRAE – American Society of Heating, Refrigeration and Air.
ASIM – American Society of Internal Medicine.
ASL – Adenylosuccinate Lyase.
ASM – American Society for Microbiology.
ASME – American Society of Mechanical Engineers.
ASON – Antisense Oligodeoxyneulceotides.
ASPEC – Association pour la Prevention et l’Etudie de la Contamination.
ASQC – American Society for Quality Control: ANSI/ASQC Q90 – US counterpart to ISO 9000
and used as an extension to the cGMPs. ASTC – Advanced Semiconductor Testing Center.
ASTM – American Society for Testing and Materials.
ASTPHLD – American Society of Territory and Public Health Laboratory
BENOR-ANI – Accredited Organizations of Belgium: ISO 9000 Accreditation Body.
BIER – Biological Indicator Evaluation Resistometer.
BIO – Biotechnology Industry Organization.
BLV – Bovine Leukemia Virus.
BoB – Bureau of Biologics.
BOC – British Oxygen Corporation.
BOD – Biological Oxygen Demand.
BOM – Bill of Materials. 53 BPAC – Blood Products Advisory Committee (advisory committee to the
FDA).
BPC – Bulk Pharmaceutical Chemicals.
BPR – Business Process Reengineering.
BSA – Bovine Serum Albumin.
BSE – Bovine Spongiform Encephalopathy.
BSI – British Standards Institute. BSL1-LS – Biosafety Level 1 – Large Scale (Also BSL2-LS &
BSL3-LS).

CAPA – Corrective and Preventative Action

CCC – Concordance Correlation Coefficient
CDRH – Center for Devices and Radiological Health. CMV – Cytomegalovirus, Human.
CPP – Critical Process Parameter
CQA – Critical Quality Attribute

DAR–TGS – National Accreditation Councils of Germany (ISO 9000 Accreditation Body).

DBA – Division of Blood Applications: Reviews ELAs for Blood Banks and Plasma Centers.
DBMS – Database Management Systems. 72
DCLD – Division of Clinical Laboratory Devices (FDA group).
DCS – Dichlorosilane.
DDDA – Dangerous Drugs Distribution Act.
DEL – Division of Establishment Licensing: Division of OELPS, Division of FDA/CBER.
DFU – Data Forcasting Units. 72
DGGE – Denaturing Gradient Gel Electrophoresis.
DHDA – Directed Heteroduplex Analysis: A modification of the heteroduplex assay, which is
designed to detect the electrophoretic retardation of a heteroduplex molecule resulting from
hybridization of target and probe DNAs that differ in sequence. Useful in PCR (Type 2) artifact
discrimination and rapid genotyping in human populations. This should have widespread utility in
differentiating closely related organisms of medical and public health importance through
identification of DNA sequence polymorphisms.
DHR – Device History Record.
DHSS – Department of Health and Social Security: Former name for the British FDA, see MCA.
DIA – Drug Information Association.
DIN – Deutsches Institut for Normung (German Institute for Standardization).
DM – Direct Material: Material used in making, bottling or labeling of product.
DMR – Device Master Record: All documentation required to produce a product.
DOE – Design of Experiment
DS – Design Space
EIR – Establishment Inspection Report: Written by an FDA inspector after an inspection is
concluded. It contains details of the inspection and closing discussion with the firm’s management.
Will contain Observations of Questionable Significance, which are not listed on the 483.
EIS – Environmental Impact Statement.
ELA – Establishment License Application.
ELISA – Enzyme Linked Immunosorbant Assay. EMA – European Medicines Agency: New
regulatory group to begin operations in January 1995, to reduce the number of licenses required to
market products within the EU. EMC – Electromagnetic Compatibility.
EMCV – Encephalomyocarditis Virus.
EMEA – European Agency for the Evamuation of Medicinal Products: A newly created central
FDA-type agency withing the EC.
EMF – Electro-motive Force: The electrocal potential difference developed by sources of energy in
electrical circuits.
EMI – Electromagnetic Interference.
EPA – Environmental Particulate Aggregates (“Dust Bunnies”).
EPFA – European Plasma Fractionation Association.
EPI – Essential Prescribing Information: CDRH term for the information that is to be part of IVD
labeling.
ERP – Enterprise Resource Planning.
ESACT – European Society for Animal Cell Technology.
ESD – Electrostatic Discharge. ESMS – Electrospray Mass Spectrometry. EtO – Ethylene Oxide:
Gaseous sterilant medium.

FMEA – Failure Modes and Effects Analysis

FONSI – Finding of No Significant Impact, on the basis of FDA analysis of the EA.
FRUO – For Research Use Only: A product that has no license.

GALP – Good Automated Laboratory Practice: Extension of GLP’s. GAMP – Good Automated
Manufacturing Practice.
GATT – General Agreement on Tariffs and Trade: Global trade agreement involving 115
countries. Entered into force January 1, 1948. Also denotes the regulating body that was renamed
WTO (World Trade Organization) in 1994.
G FP – Green Fluorescent Protein: A new reporter gene that exhibits intrinsic fluorescense.
GLP – Good Laboratory Practice.
GLSP – Good Large Scale Practice.
GRIN – Genetic Resourses Information Network.
GRMS – Gravity Root Mean Squared.
GSC – Genetic Systems Corporation.
GUI – Graphical User Interface.

HA – Hydroxyapatite: Calcium Phosphate coating on surgical, hard-tissue implants.

HACCP – Hazard Analysis and Critical Control Point: Program relies upon preventative
(Proactive) controls that focus on likely hazards, with monitoring at the critical control points in the
production chain. The FDA has a 7-step process for implementation of the procedure. Identify
hazards, identify critical control points, establish “critical limits”, establish monitoring procedures,
establish “corrective action plans”, establish effective record keeping, establish system-wide
verification.
HALT – Highly Accelerated Life Testing. HASS – Highly Accelerated Stress Screening (form of
failure analysis)

ISO – International Organization for Standardization

ISO 9000 series – Standards for installation and maintenance of a Quality System. What to do, not
how to do it. How is up to the individual company.
ISO 9001 – Quality Systems: Model for quality assurance in design, development, production,
installation and servicing.
ISO 9002 – Quality Systems: Model for quality assurance in production, installation and
servicing.
ISO 9003 – Quality Systems: Model for quality assurance in final inspection and test.
ISO 9004 – Quality Management and Quality System Elements Guideline.
ISO 10011 – Quality Assurance Auditing Guidelines, General.
ISO 10012 – Quality Assurance Auditing Guidelines for Equipment.
ISO 10013 – International Standard for Quality Manuals (Draft).
ISO 13485 – Draft document that combines ISO 9000 and EN46000.

LIF – Lasar-Induced Fluoresence: A highly sensitive methodology that, in combination with

computer software, offers a means of automating post-PCR analysis.
LIMS – Laboratory Information Management System.
LNS – Laboratoire National de la Santé (French version of FDA).
LPCVD – Low-Pressure Chemical Vapor Deposition: Process used in MEMS technology.
LRD – LIMS Raw Data: Original observations recorded by the LIMS that are needed to verify,
calculate or derive data that are or may be reported.
LTM – Light Transmission Microscope.
LTPD – Lot Tolerance Percent Defectives: Describes what a sampling plan usually rejects (the
percentage defective with a 10% chance of acceptance.)
LTR – Long Term Redundancies
LTR – Long Terminal Repeat.
LVP – Large Volume Parenteral: Injectable theraputic or nutritional products in volumes >100 ml.

MAb – Monoclonal Antibody(ies).

MAI – Medical Action Industries: OEM/manufacturer of medical supplies
MAL – Microbial Assurance Level: A level of product sterility similar to SAL.
MAP – Mouse Antibody Production.
MASAC – Medical and Advisory Committee.
MBO – Management By Objective
MBR – Master Batch Record.
MCA – Medicines Control Agency: New name for the British version of the FDA.

MRB – Materials Review Board.

MRP – Materials Requirements Planning. 72
MRPII – Manufacturing Resources Planning. 72
MTBF – Mean Time Between Failures: Mean Life of a component, or Rate of Failure.
MVC – Minimum Valid Concentration: Product concentration at the MVD.
MVD – Minimum Valid Dilution: Dilution beyond the point of being able to detect the endotoxin limit.

NACCB – National Accreditation Council for Certification Bodies (UK, ISO 9000 Accreditation
Body).
National Accreditation Council of Belgium (ISO 9000 Accreditation Body). North American Free
Trade Agreement (entered into force January 1, 1994).
NAC-QS–
NAFTA –
NAI – No Action Indicated: An Inspection Branch Conclusion drawn by the supervisory inspector
following an FDA inspection on what level of action is need to be taken against the firm. A
classification used by FDA inspectors where no corrective action is required.
NAmSA – North American Science Associates.
NANB – Non-A-Non-B Hepatitis (a.k.a. Hepatitis C).
NAPWA – The National Association of People with AIDS. Australian Accreditation Association (ISO
9000 Accreditation Body).
NATA –
NCCLS – National Committee for Clinical Laboratory Standards.
NCR – Non-Conformance Report.
NDA – New Drug Application.
NDAB – National Drugs Advisory Board (of Ireland).
NDIR – Non-Dispersive Infrared Detector.
NEB – New England Biolabs.
NEBB – National Environmental Balancing Bureau.
NEPA – National Environmental Policy Act: Directions for ascertaining the environmental impact
that may occur due to the manufacture, use and disposal of FDA regulated products.
NF – National Formulary: US Compendial Document defining standard drug formulas, provides
monographs for all pharmaceutical ingredients used in drug dosage forms.
NHF – National Hemophelia Foundation.
NHLBI – National Heart, Lung and Blood Institute.
NIAID – National Institute of Allergy and Infectious Diseases.
NIBSC – National Institute of Biological Standards and Control: Sets biopotency reference
standards for the determination of bioactivity of a product.
NIB-NA – National Accreditation Councils of Norway (ISO 9000 Accreditation Body).
NIH – National Institutes of Health: An agency of the U.S. Public Health Service, part of the U.S.
Department of Health and Human Services.
NIST – National Institute of Standards and Technology (formerly the National Bureau of Standards).
NK – Natural Killer (T&R cell Lymphocytes).
NLGHA – The National Lesbian and Gay Health Association.
NNI – Nederlands Normalisatie Instituut.
NOAEL – No Observable Adverse Effect Level (toxicity value).
NOR – Normal Operating Range

OEL – Occupational Exposure Limit

OTSS – Off-the-Shelf-Software
PNSU – Probability of a Non-Sterile Unit

QbD – Quality by Design

QTPP – Quality Target Product Profile

R3-NORDIC – Nordic Association for Contamination Control.

RAB – Registration Accreditation Board (US ISO 9000 Accreditation Body).
RAID – Redundant Array of Independent Disks.
RAPD – Random-amplified Polymorphic DNA.
RAPS – Regulatory Affairs Professional Society.
RDBMS – Relational Database Management System. 72
RDE – Remote Data Entry: Electronic data gathering and transmittal.

rDNA – Recombinant DNA.

SDS-PAGE – Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis.
SDWA – Safe Drinking Water Act (of 1996).
SEM – Scanning Electron Microscope (Microscopy).
SEMI – Semiconductor Equipment and Materials Institute.
SGR – Schweizerische Gesellschaft für Reinraumtechnik.
SHEAR – Safety Health and Environmental Action Request.
SIM – Society for Industrial Microbiology.
SINCERT – National Accreditation Council of Italy
SMACCNA – Sheet Metal and Air Conditioning Contractors, National Association.
SMART – Submission Management and Review Tracking Program: The FDA is developing a
comprehensive, standardized information management system to support the premarket review
process.
SMART – Specific, Measurable, Action, Realistic, Time Limited: Dale Carnegie goal setting tool.
SMCC – Sulfosuccinimidyl 4-(n-maleimidomethyl) cyclohexane-1carboxylate.
SMDA – Safe Medical Devices Act (of 1990).
SMP – Symmetric Multiprocessing. 72
SNEA – Societe Nationale Elf Aquitaine. 25 SOP – Standard Operational Procedure. SPC –
Statistical Process Control.
SPC – Stochastic Process Control
SPI – Society of the Plastics Industry, Inc.
SWEDAC – National Accreditation Council of Sweden (ISO 9000 Accreditation Body).

TAP – Tick Anti–coagulant Peptide

TBT – Technical Barriers to Trade: Agreements found in current GATT. How the USA and other
countries regulate drugs.
TC – Thermocouple.
TCGF – T-Cell Growth Factor.
TCR – T-Cell Receptor (molecules).
TdT – Terminal deoxynucleotidyl Transferase.
USAMRDALC – United States Army Medical Research Development, Acquisitions, and Logistics
Command.
USAN – United States Adopted Names: A program that is the specifically organized effort in the
United States directed to producing simple and useful nonproprietary names for drugs while the
drugs are still in the investigational stages.
USFCC – United States Federation for Culture Collections.
USP – United States Pharmacopoeia.
UTR – Uniform Temperature Reference: Device on a multi-channel temperature recorder (Kaye
Digistrips) that is used to lessen the tracking error between the cold junction temperature and the
temperature measured by the reference RTD.
UVT – Ultra-violet Transmission.

VAI – Voluntary Action Indicated: An inspection branch conclusion drawn by the supervisory
inspector following an FDA inspection on what level of action is need to be taken against a firm.
VDI – Verein Deutscher Ingenieure.
VDT – Video Display Terminal 53 (See CRT).
VIA – Volunteer Action Indicated: Classification used by FDA inspectors where corrective action
from the company is required.

WYSIWYG – What You See Is What You Get.

References: