The biological process whereby an organism adapts to a new environment. One
example is the process of developing microorganisms that degrade toxic
wastes in the environment.
Defines all areas that can influence unit operations required for
manufacturing, and relationships and flows between them.
Specifies how passwords must be defined and employed for all user accounts
on a system. It specifically addresses the issues of password aging,
password uniqueness, and locking a user account because of invalid logon
attempts. CFR 21 Part 11 mandates technical controls in these areas
A compound of an electronegative element or radical with hydrogen; it form
salts by replacing all or part of the hydrogen with an electropositive
element or radical. Or, a hydrogen-containing substance that when dissolved
in water dissociates to produce one or more hydrogen ions (H+).
Injection of an acid into a liquid stream to make it less alkaline (pH
A value set to identify when a parameter has drifted outside the operating
range (Acceptance Criteria). A documented response is usually required.
Material used to adsorb organic impurities from water. Derived from wood,
lignite, pulp-mill char, blood, etc. The source material is initially
charred at high temperature to convert it to carbon. The carbon is then "activated"
by oxidation from exposure to high temperature steam. It comes in granular
or powdered form.
The formation of an antibody that can be stimulated by infection or
Any component that is intended to furnish pharmacological activity or other
direct effect in the diagnosis, cure, mitigation, treatment, or prevention
of disease, or to affect the structure or any function of the body of man or
other animals. The term includes those components that may undergo chemical
change in the manufacture of the drug product and are present in the drug
product in a modified form intended to furnish the specified activity or
Active Pharmaceutical Ingredient
The region of a protein molecule that binds the specific substrate and
chemically modifies it into the new product (in an enzyme) or interacts with
it (in a receptor).
Energy-requiring transport of a solution across a membrane in the direction
of increasing concentration.
The quantity that is actually produced at any appropriate phase of
manufacture, processing, or packaging of a particular drug product.
A purine base, 6-aminopurine, occurring in RNA (ribonucleic acid) and DNA
(deoxyribonucleic acid) and as a component of adenosine triphosphate.
see: Adverse Drug Reaction
Adhesion of the molecules of a gas, liquid or dissolved substance to a
surface because of chemical or electrical attraction - typically
accomplished with granular activated carbon to remove dissolved organics and
chlorine. The attachment of charged particles to the chemically active
groups on the surface and in the pores of an ion exchanger.
Acquired, sporadic, accidental contaminants.
Undesired effects or toxicity due to exposure (often but not limited to a
drug or medical device).
Adverse Drug Reaction (ADR)
An undesirable effect that may be caused by a study drug.
An alarm indicating a drift of a monitored parameter toward an out-of-spec
condition. It is advisory in that no GMP violation has occurred, and is used
to advise corrective action before an action alarm can happen.
An organism that can live and grow only in the presence of oxygen.
1. Facultative aerobe: one which normally thrives in the absence of oxygen,
but which may acquire the faculty of living in the presence of oxygen.
2. Obligate aerobe: one that cannot live without air.
The plural of aerobe.
Living in air.
Bacteria capable of growing in the presence of Oxygen.
A product that is dispensed by a propellant from a metal can up to a
maximum size of 33.8 fluid ounces (1000 mL) or a glass or plastic bottle up
to a size of 4 fluid ounces (118.3 mL), other than a rim-vented container.
A gaseous suspension of fine (100µm or smaller in size) solid or
Light-scattering mass concentration indicating instrument with a threshold
sensitivity of at least 10 to the negative third power microgram per liter
for 0.3µm diameter DOP (Dioctyl Phthalate) concentrations over a range
of 10 to the fifth power times the threshold sensitivity. Photometers may
include hand-held remote meter probes that can scan for airborne
contaminants in HEPA filters, in penetrations around frames, seals and
plenums, and in hoods and work stations.
see: Auger Electron Spectroscopy
A complex mixture of polysaccharides obtained from marine red algae, used
as an emulsion stabilizer in foods, as a sizing in fabrics, as a gelling
agent and as a solid substrate or media for the laboratory culture of
microorganisms. Agar melts at 100ºC and when cooled below 44ºC
forms a stiff and transparent gel. Microorganisms are seeded and grown on
the surface of the gel.
A highly purified form of agar.
Agarose Gel Electrophoresis
A method used to separate, identify, and purify molecules of different
molecular weight and/or structure. It is specifically applied to the
separation of protein or DNA fragments where it is rapid, simple, and
accurate, and the separated molecules can be visualized directly by staining
with dyes. The electrophoretic migration rate of molecules through agarose
gel is dependent on the following parameters:
1. Molecular size: molecules pass through the gel at rates that are
inversely proportional to the log of their molecular weight.
2. Agarose concentration: a molecule of a given size migrates at different
rates through gels containing different concentrations of agarose.
3. Molecular conformation: a molecule of the same molecular weight but of a
different conformation will migrate at different rates. Generally, closed
circular or globular forms will migrate faster than linear forms.
4. Electric current: at low voltages the rate of migration is proportional
to the voltage, but as the voltage is increased the rate of migration of
high molecular weight fragments is increased differentially.
Nitrogen Trichloride (NCl3).
Suspended solids clustered together to form larger clumps or masses that
are easier to remove by filtration or settling.
The sticking together of insoluble antigens such as bacteria, viruses or
erythrocytes by a particular antibody. Agglutination assays are used to type
human blood before a transfusion.
AHF (Antihemophilic Factor)
In the clotting of blood it is also known as Factor VIII.
Airborne Particulate Cleanliness Classes
Statistically allowable number of particles equal to, or larger than 0.5µm
in size per cubic foot of air. According to ISO 14644-1, a classification
number, N, shall designate airborne particulate cleanliness.
Air Change Rate
The number of times the total air volume of a defined space is replaced in
a given unit of time. This is computed by dividing the total volume of the
subject space (in cubic feet) into the total volume of air exhausted from
(or supplied to) the space per unit of time.
Filtration systems that may be freestanding or installed in a ceiling or
wall to remove contaminants such as bacteria, viruses, and dust from the
air. Air cleaners may incorporate HEPA filters.
Using chemical smoke or fog to visualize flow patterns in a cleanroom or
A reactor in which the source of agitation is air sparged upwards through a
draft tube - most widely used for cell culture applications and monoclonal
A room or space designed to act as a means of segregating areas of
different air classification or quality. It may contain a method to remove
particulate contamination from clean room garments as personnel pass
through, and usually includes HEPA filtered air supply and interlocking
doors. Airlocks pressure will "float" between those of the spaces
being protected. With all doors closed, the airlock pressure will be
somewhere between that of the highest adjoining room and that of the lowest
adjoining room as air flows through it from room to room. "Ventilated
airlocks" are in neutral ducted air balance (supply CFM = return CFM).
Air Velocity Meters/Monitors
Meters to measure and indicate the force and speed of airflow. Meters may
use a variety of probes for measuring near HEPA filters and at right angles.
Monitors check and record air velocity.
Audible or visual signals used to warn of unacceptable conditions at
monitored sites. They may be buzzers, horns, speakers, bells, or warning
lights. They can be Advisory, Alert, or Action alarms. The first two are for
operation and maintenance information, to alert of abnormal situations that
do not compromise product SISPQ. The Action alarm is for GMP records,
indicating that product SISPQ may have been compromised, but Alert alarms
are also usually recorded.
Commonly, the white of egg is a simple protein widely distributed
throughout the tissues and fluid of plants and animals. Soluble in pure
water it is also precipitable from a solution by mineral acids, and
coagulable by heat in acid or neutral solution.
Resembling albumin, a simple protein present in horny and cartilaginous
tissues, insoluble in neutral solvents. Keratin, elastin, and collagen are
Used in determining when a parameter is drifting toward extremes of the
Of, pertaining to, or designating an exact divisor or factor of a quantity,
specially of an integer. To divide out a sample to multiple containers for
multiple analytical tests.
An expression of the total amount of basic anions (hydroxyl groups) present
in a solution. In water analysis, it also represents the presence of
carbonate, bicarbonate, and occasionally borate, silicate, and phosphate
salts that react to produce hydroxyl groups. Bicarbonate and carbonate ions
are expected to be in most waters. Hydroxide may occur in water that has
been softened by the lime soda process or has been in contact with fresh
concrete. Alkalinity furnishes a guide in choosing appropriate treatment of
either raw water or plant effluents.
The clear white portion of an egg. In influenza vaccine manufacturing, the
virus is propagated in the embryonic chick and sloughed into the allantoic
fluid that is harvested to produce the vaccine.
Alternative form of a genetic locus; a single allele for each locus is
inherited separately from each parent (e.g., at a locus for eye color the
allele might result in blue or brown eyes)
An extract in a solvent of a substance that causes an allergic reaction.
They are relative crude drugs by contemporary standards and are manufactured
by specialty companies and in some cases, by a practicing allergist. Also,
allergenic extracts are generally difficult to filter since they most
frequently are extracts of natural substances such as foods, house dust,
animal hair, etc.
Aluminum sulfate, commonly added during municipal water treatment to cause
insoluble colloids to coalesce into larger particles that can be removed by
A disease that causes memory loss, personality changes, dementia and,
ultimately, death. Not all cases are inherited, but genes have been found
for familial forms of Alzheimer's disease.
The normal environment conditions such as temperature, relative humidity,
or room pressure of a particular area under consideration.
A simple bacterial test for carcinogens.
A substance that may be derived from ammonia by the replacement of one or
more of the hydrogen atoms by hydrocarbon radicals.
Any of a group of twenty hydrocarbon molecules (containing the radical
group NH2) linked together in various combinations to form proteins in
living things. Synthesized by living cells or obtained as essential
components of the diet of human and animals, these twenty amino acids are
divided into four (4) groups on the basis of their side-chain properties:
1. Neutral, hydrophobic side chains,
2. Neutral, hydrophilic side chains,
3. Acid, hydrophilic side chains,
4. Basic, hydrophilic side chains.
In addition to the twenty common amino acids there are less common
derivatives (e.g. hydroxyproline, found in collagen) formed by the
modification of a common amino acid.
Amphoteric electrolyte. Electrolyte that can either give up or take on a
hydrogen ion and can thus behave as either an acid or a base.
Having two opposite characteristics.
An antibiotic widely used in clinical treatment and rDNA research. It is a
derivative of penicillin, which kills bacteria by interfering with the
synthesis of the cell wall.
An increase in the number of copies of a specific DNA fragment; can be In
Vivo or In Vitro.
The production of additional copies of a chromosomal sequence, found as
either intrachromosomal or extrachromosomal DNA.
Ampoule or Ampule
A small glass vial sealed after filling and one of the earliest devices
developed for safe storage of sterile injectable unit.
Amyotrophic Lateral Sclerosis
An inherited, fatal degenerative nerve disorder, also known as Lou Gehrig's
The intracellular process involved in the synthesis of more complex
compounds than those involved in catabolism (for example, glucose to
glycogen) and requires energy.
A microorganism that thrives best, or only, when deprived of oxygen.
1. Facultative anaerobe: one able to grow in the presence or absence of
2. Obligate or obligatory anaerobe: one that will grow only in the absence
of free oxygen.
Relating to an anaerobe.
Bacteria capable of growing in the absence of Oxygen.
Pertaining to data that consists of continuously variable physical
Analytical Data Interchange (ANDI)
A generic file format. It was common practice before CFR 21 Part 11 to save
information from analytical instruments in this file format. The
disadvantage now is that the approach does not allow replaying of data on a
different system to yield the same result.
Small scale process used to characterize and/or separate a mixture, a
compound, or an unknown material into its constituent parts or elements.
Material used in preparing drugs that does not become a component of the
drug (e.g. steam, air, N2, DI water).
A device that measures air speed.
A unit of length equal to one hundred-millionth of a centimeter (one
ten-thousandth of a micron) used especially to specify radiation
A negatively charged particle or ion.
Anion Exchange Resin
An ion exchange material that removes anions from solution by exchanging
them with hydroxyl ions.
The process by which the complementary base pairs in DNA strands combine.
A treatment process for steel in which the metal is heated and held at a
suitable temperature and then cooled at a suitable rate for the purpose of
reducing hardness, improving machinability, facilitating cold working,
producing a desired microstructure, or obtaining desired mechanical,
physical, or other properties.
An organic substance of microbial origin (usually mold or actinomycete
bacteria) that is either toxic or growth inhibiting for other organisms.
Also with the advent of synthetic methods of production, a substance
produced by a microorganism or a similar substance (produced wholly or
partly by chemical synthesis) which, in low concentrations, inhibits the
growth of other microorganisms. Penicillin, tetracycline, and erythromycin
are examples of antibiotics.
A modified protein molecule present in the blood serum or plasma (and other
body fluids), whose activity is associated chiefly with gamma globulin.
Produced by the immune system in response to exposure to a foreign
substance, it is the body's protective mechanism against infection and
disease. An antibody is characterized by a structure complementary to the
foreign substance, the antigen that provokes its formation, and is thus
capable of binding specifically to the foreign substance to neutralize it.
Any of various foreign substances such as bacteria, viruses, endotoxins,
exotoxins, foreign proteins, pollen, and vaccines, whose entry into an
organism induces an immune response (antibody production, lymphokine
production, or both) directed specifically against that molecule. Response
may be demonstrated as an increased reaction, such as hypersensitivity
(usually protein or a complex of protein and polysaccharide, or occasionally
a polysaccharide of high molecular weight), a circulating antibody that
reacts with the antigen, or some degree of immunity to infectious disease if
the antigen was a microorganism or its products.
An antibody to an interferon. Used for the purification of interferons.
Acting against sepsis. An antiseptic agent is one that has been formulated
for use on living tissue such as mucous membranes or skin to prevent or
inhibit growth or action of organisms. Antiseptics should not be used to
decontaminate inanimate objects.
The blood serum obtained from an animal after has been immunized with a
particular antigen. It contains antibodies specific for that antigen as well
as antibodies specific for any other antigens with which the animal has
previously been immunized.
Reducing static electric charges by retaining enough moisture to provide
Liquid cleaners that enhance surface conductivity of cleanroom tabletops,
workstations, and other surfaces.
An antibody that is capable of neutralizing the specific toxin that
stimulated its production in the body. Antitoxins are produced in animals
for medical purposes by injection of a toxin or toxoid, with the resulting
serum being used to counteract the toxin in other individuals.
API (Active Pharmaceutical Ingredient)
Also called 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 a drug becomes an active ingredient of the drug
product. Such substances are intended to furnish pharmacological activity or
other direct effect in the diagnosis, cure, mitigation, treatment, or
prevention of disease or to affect the structure and function of the body.
API Starting Material
A material used in the production of an API which is itself or is
incorporated as a significant structural fragment into the structure of the
API. A starting material may be an article of commerce, a material purchased
from one or more suppliers under contract or commercial agreement, or it may
be produced in-house. Starting materials are normally of defined chemical
properties and structure.
The protein moiety of an enzyme - determines the specifity of the enzyme
Any executable program developed or modified specially for customer
Appropriated login or Impersonation
Someone using the authorization code, usually user ID and password of
another person to secure access to network resources for which he or she
does not have privileges or authorization. Can be intentional or not. CFR 21
Part 11 mandates technical controls that prevent this.
An underground layer of permeable rock, sand, or gravel that contains water
for wells or springs.
Arithmetic Average Roughness (Ra)
The arithmetic average height of roughness component irregularities from
the mean line measured within the sample length (L). This measurement
conforms to ANSI/ASME B46.1 "Surface Texture - Surface Roughness,
Waviness and Lay". Ra (formerly known as AA or Arithmetic Average in
the U.S., and CLA Centerline Average in the U.K.) is usually expressed in
microinches (µin), and performed by moving a stylus or profilometer in
a straight line along the surface. A consistent and measurable surface
finish can be specified for a desired roughness i.e., 9-11 microinch.
ISO 14644-1 defines the "as built" occupancy state as "condition
where the installation is complete with all services connected and
functioning but with no production equipment, materials, or personnel
A family of fungi marked by long spore-containing cells. Form sexual spores
called ascospores, which are contained within a sac (a capsule structure).
Ergot, truffles, some molds of the genera Neurospora and Aspergillus, and
yeasts belong to this category.
A condition in which living pathogenic (causing or capable of causing
disease) organisms are absent.
Marked by or relating to asepsis.
Processing conditions designed to achieve a sterile product.
Aseptic Processing Area
Area in which sterile product is formulated, filled into containers, and
Aseptic Transfer (in Isolators)
The key issue in all contained aseptic environments. Aseptic transfer is
essential for change parts, components, and even product to enter and exit
an isolator system without sterility challenges. There are an increasing
number of ways to make an aseptic transfer. The following is a brief list of
some of the key techniques:
1. Alpha Beta Systems Double Door Systems: also called RTPs (Rapid Transfer
Ports) and HCT (High Containment Transfer). When mated, the two ports act as
one door, protecting the internal and external environments.
2. Alpha Beta Dry Heat Sterilized: similar to Alpha Beta port with the
additional safeguard of a heat sterilized seal.
3. UV and Pulsed Light: light sterilization/sanitization. Sterilizing the
system by making use of a wide spectrum of light within the transfer
4. One Shot Systems: basically, two halves coming together. Similar to an
Alpha Beta port but simpler, cheaper, and capable of only a single
5. Heat Welded Bag Systems: passed in or passed out using a continuous
polyethylene liner which is heat sealed and cut to maintain the integrity of
the internal and external environments.
6. Steam Sterilized: the liquid component or powder path is clean steam
sterilized after connection and prior to transfer.
7. Autoclave/Depyrogenation/Dryheat: pass through for batch. Use of
conventional autoclave to sterilize a canister provided with an Alpha Beta
port and filters to allow the passage of steam and safe aspiration on
cooling. Depyrogenation/Dryheat uses dry heat to sterilize and at sufficient
temperature depyrogenate components, typically glassware, in a batch oven
8. Depyrogenation Tunnel: standard volume glassware entry.
Depyrogenation/Dry heat uses dry heat to sterilize and at sufficient
temperature to depyrogenate components, typically glassware, in a tunnel
allowing continuous input.
ASME Bioprocessing Equipment (BPE- 1997)
An American National Standard that covers, either directly or by reference,
requirements for materials, design, fabrication, examination, inspection,
testing, certification (for pressure systems), and pressure relief (for
pressure systems) of vessels and piping for bioprocessing systems, including
sterility and cleanability (Part SD), dimensions and tolerances (Part DT),
surface finish requirements (Part SF), material joining (Part MJ), and
equipment seals (Part SG) for the bioprocessing systems in which the
pressure vessels and associated piping are involved. This Bioprocessing
Equipment (BPE) Standard does not address all aspects of these activities,
and those aspects that are not specifically addressed should not be
Requirements of this Standard apply to:
1. All parts that contact the product, raw materials, and/or product
intermediates during manufacturing, process development, or scale-up.
2. All equipment or systems that are critical part of product manufacture,
such as Water For Injection (WFI), clean steam, ultrafiltration,
intermediate product storage, and centrifuges. ASME/ANSI B31 Code for
A number of individually published Sections, each an American National
Standard. Rules for each Section reflect the kinds of piping installations
considered during its development, as follows:
1. B31.1 Power Piping: piping typically found in electric power generating
stations, in industrial and institutional plants, geothermal heating
systems, and central and district heating and cooling systems.
2. B31.3 Process Piping: piping typically found in petroleum refineries,
chemical, pharmaceutical, textile, paper, semiconductor, and cryogenic
plants, and related processing plants and terminals. Certain piping within a
facility may be subject to other codes and standards, including but not
limited to: (a) ANSI Z223.1 National Fuel Gas Code: piping for fuel gas from
the point of delivery to the connection of each fuel utilization device. (b)
NFPA Fire Protection Standards: fire protection systems using water, carbon
dioxide, halon, foam, dry chemical, and wet chemicals. (c) NFPA 99 Health
Care Facilities: medical and laboratory gas systems. (d) Building and
plumbing codes, as applicable, for potable hot and cold water, and for sewer
and drain systems.
3. B31.4 Pipeline Transportation Systems for Liquid Hydrocarbons and Other
Liquids: piping transporting products that are predominately liquids between
plants and terminals and within terminals, pumping, regulating, and metering
4. B31.5 Refrigeration Piping: piping for refrigerants and secondary
5. B31.8 Gas Transportation and Distribution Piping Systems: piping
transporting products that are predominately gas between sources and
terminals, including compressor, regulating, and metering stations; gas
6. B31.9 Building Services Piping: piping typically found in industrial,
institutional, commercial, and public buildings, and in multi-unit
residences, which does not require the range of sizes, pressures, and
temperatures covered in B31.1.
7. B31.11 Slurry Transportation Piping Systems: piping transporting aqueous
slurries between plants and terminals and within terminals, pumping, and
A technique (test) for measuring a biological response or for determining
characteristics such as composition, purity, activity, and weight.
The formation of cellular material utilizing small food molecules and
Atmospheric Tank (Fire Code)
A storage tank designed to operate at pressures from atmospheric through
0.5 pounds per square inch (psig) (3.4 kPa).
Atomic Absorption Spectrophotometry
A highly sensitive instrumental technique for identifying and measuring
metals in water.
HVAC room condition when unmanned, and without machinery operating.
Previously called "static condition".
ISO 14644-1 defines "at rest" occupancy state as "condition
where the installation is complete with equipment installed and operating in
a manner agreed upon by the customer and supplier, but with no personnel
European Community (EC) defines "at rest" state as "the
condition where the installation is complete with production equipment
installed and operating but with no operating personnel present". The
Medicines Inspectorate, however, further clarifies, "It should normally
be taken to mean that ventilation systems are operating and other equipment
is present in an operational condition but not in use".
A feature of the audit trail that aids both originator and reviewer in
understanding why the originator performed a specific action. CFR 21 Part 11
does not require entering the reason for a record change, but some predicate
rules (such as GLPs) do expect an explanation. It is important that the user
interface for entering audit comments prevents users from changing the audit
A computer-generated and time-stamped record of who did what, when. CFR 21
Part 11 requires audit trails to be generated independently of operators. An
audit trail must capture all activities related to creating, modifying, and
destroying records on a system.
Auger Electron Spectroscopy (AES)
An alternative surface analysis that can detect all elements with an atomic
number greater than that of helium with the additional ability to analyze
sub micron-diameter features. It is not as quantitative as ESCA and cannot
determine the chemical state of an element. The primary advantage of Auger
is that when combined with etching, a chemical depth profile can be measured
rapidly and can image the distribution on the surface of spatial limitation
resolution of 100 to 1,000 angstroms (depending on the equipment
A face-centered cubic crystal with high solubility for carbon (about 2%);
an allotropic form of iron resulting from steel being heated above the
A weld made by fusion of the base material without the addition of filler.
The process of identifying a person, system, or company sufficiently to
allow access to a system or part of a system.
Also known as authority checks, or authorized signers are mechanisms
distinct from authorization that grants or denies access to a network
resource, authentication programs are used by system administrators to
establish and verify as conclusively as possible that a person logging in to
the network is who he or she claims to be. FDA says that "authority
checks" are to "ensure that only authorized individuals can use
the system, electronically sign a record, access the operation or computer
system, input or output device, alter a record, or perform operations".
An apparatus into which moist heat (steam) under pressure is introduced to
sterilize or decontaminate materials placed within (e.g. filter assemblies,
glassware, etc.). Steam pressure is maintained for pre-specified times and
then allowed to exhaust. There are two types of autoclaves:
1. Gravity displacement autoclave: this type of autoclave operates at 121ºC.
Steam enters at the top of the loaded inner chamber, displacing the air
below through a discharge outlet.
2. Vacuum autoclave: this type of autoclave can operate with a reduced
sterilization cycle time. The air is pumped out of the loaded chamber before
it is filled with steam.
Auto Immune Disease
A disease in which the body produces an immunogenic response against
self-antigens. In some cases, predominantly one organ is affected (e.g.
hemolytic anemia and chronic thyroiditis); in others, the disease process is
diffused through many tissues (e.g. SLE (Systemic Lupus Erythematosis)).
Any facility system or piece of equipment that is controlled with limited
or no manual intervention.
Welding with equipment that performs the welding operation without
adjustment of the controls by a welding operator. The equipment may or may
not perform the loading and unloading of the work.
A technique that uses X-ray film to visualize radioactively labeled
molecules or fragments of molecules; used in analyzing length and number of
DNA fragments after they are separated by gel electrophoresis.
A chromosome not involved in sex determination. The diploid human genome
consists of 46 chromosomes, 22 pairs of autosomes, and 1 pair of sex
One of two categories in which microorganisms are classified on the basis
of their carbon source. Autotrophs use carbon dioxide as a carbon source.