A
Acclimatization
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.
Accommodation
Schedule
Defines all areas
that can influence
unit operations required
for manufacturing,
and relationships
and flows between
them.
Account
Policy
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 specifically.
Acid
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+).
Acid
Feed
Injection of an acid
into a liquid stream
to make it less alkaline
(pH adjustment).
Action
Point
A value set to identify
when a parameter has
drifted outside the
operating range (Acceptance
Criteria). A documented
response is usually
required.
Activated
Carbon
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.
Active
Immunity
The formation of an
antibody that can
be stimulated by infection
or vaccination.
Active
Ingredient
Any component that
is intended to furnish
pharmacological activity
or other direct effect
in the diagnosis,
cure, mitigation,
treatment, or prevention
of disease, or to
affect the structure
or any function of
the body of man or
other animals. The
term includes those
components that may
undergo chemical change
in the manufacture
of the drug product
and are present in
the drug product in
a modified form intended
to furnish the specified
activity or effect.
Active
Pharmaceutical Ingredient
Active
Site
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).
Active
Transport
Energy-requiring transport
of a solution across
a membrane in the
direction of increasing
concentration.
Actual
Yield
The quantity that
is actually produced
at any appropriate
phase of manufacture,
processing, or packaging
of a particular drug
product.
Adenine
(A)
A purine base, 6-aminopurine,
occurring in RNA (ribonucleic
acid) and DNA (deoxyribonucleic
acid) and as a component
of adenosine triphosphate.
ADR
see: Adverse Drug
Reaction
Adsorption
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.
Adventitious
Agents
Acquired, sporadic,
accidental contaminants.
Adverse
Agents
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.
Advisory
Alarm
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.
Aerobe
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.
Aerobia
The plural of aerobe.
Aerobic
Living in air.
Aerobic
Bacteria
Bacteria capable of
growing in the presence
of Oxygen.
Aerobion
see: Aerobe
Aerosol
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.
Aerosol
A gaseous suspension
of fine (100µm or
smaller in size) solid
or liquid particles.
Aerosol
Photometer
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.
AES
see: Auger Electron
Spectroscopy
Agar
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.
Agarose
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.
Agene
Nitrogen Trichloride
(NCl3).
Agglomerate
Suspended solids clustered
together to form larger
clumps or masses that
are easier to remove
by filtration or settling.
Agglutination
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.
Air
Cleaners
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.
Airflow
Visualization
Using chemical smoke
or fog to visualize
flow patterns in a
cleanroom or clean
space.
Air-Lift
Bioreactor
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 antibody
production.
Airlock
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.
Alarms
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.
Albumin
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.
Albuminoid
Resembling albumin,
a simple protein present
in horny and cartilaginous
tissues, insoluble
in neutral solvents.
Keratin, elastin,
and collagen are albuminoids.
Alert
Point
Used in determining
when a parameter is
drifting toward extremes
of the operating range.
Aliquot
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.
Alkalinity
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.
Allantoic
Fluid
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.
Allele
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)
Allergenic
Extract
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.
Alum
Aluminum sulfate,
commonly added during
municipal water treatment
to cause insoluble
colloids to coalesce
into larger particles
that can be removed
by settling.
Alzheimer's
Disease
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.
Ambient
The normal environment
conditions such as
temperature, relative
humidity, or room
pressure of a particular
area under consideration.
Ames
Test
A simple bacterial
test for carcinogens.
Amine
A substance that may
be derived from ammonia
by the replacement
of one or more of
the hydrogen atoms
by hydrocarbon radicals.
Amino
Acids
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.
Ampholyte
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.
Amphoteric
Having two opposite
characteristics.
Ampicillin
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.
Amplification
An increase in the
number of copies of
a specific DNA fragment;
can be In Vivo or
In Vitro.
Amplification
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 disease.
Anabolism
The intracellular
process involved in
the synthesis of more
complex compounds
than those involved
in catabolism (for
example, glucose to
glycogen) and requires
energy.
Anaerobe
A microorganism that
thrives best, or only,
when deprived of oxygen.
1. Facultative anaerobe:
one able to grow in
the presence or absence
of free oxygen.
2. Obligate or obligatory
anaerobe: one that
will grow only in
the absence of free
oxygen.
Anaerobic
Relating to an anaerobe.
Anaerobic
Bacteria
Bacteria capable of
growing in the absence
of Oxygen.
Analog
Pertaining to data
that consists of continuously
variable physical
qualities.
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.
Analytical
Method
Small scale process
used to characterize
and/or separate a
mixture, a compound,
or an unknown material
into its constituent
parts or elements.
Ancillary
Material
Material used in preparing
drugs that does not
become a component
of the drug (e.g.
steam, air, N2, DI
water).
ANDI
Anemometer
A device that measures
air speed.
Angstrom
(?)
A unit of length equal
to one hundred-millionth
of a centimeter (one
ten-thousandth of
a micron) used especially
to specify radiation
wavelengths.
Anion
A negatively charged
particle or ion.
Anion
Exchange Resin
An ion exchange material
that removes anions
from solution by exchanging
them with hydroxyl
ions.
Anneal
The process by which
the complementary
base pairs in DNA
strands combine.
Annealing
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.
Antibiotic
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.
Antibody
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.
Antigen
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.
Anti-interferon
An antibody to an
interferon. Used for
the purification of
interferons.
Antiseptic
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.
Antiserum
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.
Antistatic
Reducing static electric
charges by retaining
enough moisture to
provide electrical
conduction.
Antistatic
Cleaners
Liquid cleaners that
enhance surface conductivity
of cleanroom tabletops,
workstations, and
other surfaces.
Antitoxin
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.
Apoenzyme
The protein moiety
of an enzyme - determines
the specifity of the
enzyme reaction.
Application
Software
Any executable program
developed or modified
specially for customer
applications.
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.
Aquifer
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.
"As-Built"
Cleanroom
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 present".
Ascomycetes
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.
Asepsis
A condition in which
living pathogenic
(causing or capable
of causing disease)
organisms are absent.
Aseptic
Marked by or relating
to asepsis.
Aseptic
Processing
Processing conditions
designed to achieve
a sterile product.
Aseptic
Processing Area
Area in which sterile
product is formulated,
filled into containers,
and sealed.
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
chamber.
4. One Shot Systems:
basically, two halves
coming together. Similar
to an Alpha Beta port
but simpler, cheaper,
and capable of only
a single connection.
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 considered prohibited.
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 Pressure Piping
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
stations.
4. B31.5 Refrigeration
Piping: piping for
refrigerants and secondary
coolants.
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 gathering pipelines.
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 regulating
stations.
Assay
A technique (test)
for measuring a biological
response or for determining
characteristics such
as composition, purity,
activity, and weight.
Assimilation
The formation of cellular
material utilizing
small food molecules
and energy.
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.
At
Rest
HVAC room condition
when unmanned, and
without machinery
operating. Previously
called "static condition".
"At-Rest"
Cleanroom
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
present".
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".
Audit
Comment
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 trail itself.
Audit
Trail
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 capability).
Austenite
A face-centered cubic
crystal with high
solubility for carbon
(about 2%); an allotropic
form of iron resulting
from steel being heated
above the transformation
temperature.
Autegoneous
Weld
A weld made by fusion
of the base material
without the addition
of filler.
Authentication
The process of identifying
a person, system,
or company sufficiently
to allow access to
a system or part of
a system.
Authentication
Mechanisms
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".
Autoclave
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)).
Automated
System
Any facility system
or piece of equipment
that is controlled
with limited or no
manual intervention.
Automatic
Welding
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.
Autoradiography
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.
Autosome
A chromosome not involved
in sex determination.
The diploid human
genome consists of
46 chromosomes, 22
pairs of autosomes,
and 1 pair of sex
chromosomes.
Autotrophs
One of two categories
in which microorganisms
are classified on
the basis of their
carbon source. Autotrophs
use carbon dioxide
as a carbon source.
B
BAC
(Bacterial Artificial
Chromosome)
A vector used to clone
DNA fragments (100-kb
to 300-kb insert size;
average, 150-kb) in
E. Coli cells. Based
on naturally occurring
F-factor plasmid found
in the bacterium E.
coli.
Background
Contamination
Contamination introduced
accidentally in reagents,
dilution water, solvents,
rinse water, etc.,
which can be confused
with constituents
in samples being analyzed.
Background
Environment
The environment that
surrounds a critical
area.
Back-up Copy
A magnetic copy of
data, software, user-developed
application, or operating
parameters associated
with an automated
system and not considered
the original.
Backward
Compatibility
A new version of a
computer program that
can use files and
data created with
an older version of
the same program.
A computer is said
to be backward compatible
if it can run the
same software as the
previous model. Backward
compatibility is important
because it eliminates
the need to start
over when you upgrade
to a newer product,
but is sometimes sacrificed
in favor of a new
technology.
Backwash
The countercurrent
flow of water through
equipment, usually
to clean or to recover
performance, such
as in a resin bed
(flow-in at the bottom
of the exchanger unit
and out at the top)
to clean and reclassify
the bed after exhaustion.
This process of reversing
flow may also be applied
to filters in order
to force contaminants
out of plugged pores
and passages.
Bacteria
The plural of Bacterium.
Bactericide
An agent that kills
vegetative bacteria
but not mycobacteria
or spores.
Bacteriophage
A virus that exclusively
infects bacteria.
A protein coat surrounds
the genome (DNA or
RNA). One of the bacteriophages
most extensively studied
is the lambda phage,
which is also one
of the most important
viral vectors used
in rDNA work. Lambda
promoters have been
used to express eukaryotic
proteins in E.coli.
Bacteriostatic
Inhibiting growth
of bacterial organisms
without necessarily
killing them or their
spores.
Bacteriostatic
Water
For Injection, U.S.P.
Water that serves
the same purposes
as Sterile Water for
Injection, it meets
the same standards,
with the exception
that it may be packaged
in either single-dose
or multiple-dose containers
of not larger than
30-mL size.
Bacterium
Any of a large group
of microscopic organisms
having round, rod-shaped,
spiral, or filamentous
unicellular or noncellular
bodies that are often
aggregated into colonies,
are enclosed by a
cell wall or membrane
(prokaryotes), and
lack fully differentiated
nuclei. Bacteria range
in size from 0.4µm
to 2.0µm and may exist
as free-living organisms
in soil, water, organic
matter, or as parasites
in the live bodies
of plants. Some are
disease producing,
but most perform necessary
functions such as
digestion, fermentation,
and nitrification.
Most of the forms
are variously grouped
under generic names
such as: Alcaligenes,
Dialister, Escherichia,
Klebsiella, Kurthia,
Pasteurella, Salmonella,
and Shigella.
Barometer
Instrument
used to measure atmospheric
pressure.
Barrier Isolator
A containment device
that utilizes barrier
technology for the
enclosure of a controlled
workspace. There are
two main types of
isolator: 1. Type
1 Isolator: An isolator
designed to protect
the product from process-generated
and external factors
that would compromise
its quality. 2. Type
2 Isolator: An isolator
designed to protect
the product from process-generated
and external factors
that would compromise
its quality and to
protect the operator
from hazards associated
with the product.
Barrier Technology
The technology of
using separating environments,
whether protecting
the world from a product
or the product from
the world. Containment,
barrier isolation
and isolation all
refer to the same
technology, which
is enclosing an environment.
There are, however,
some redefining terms
that are gaining favor:
1. Containment - protect
the world from the
product (as in the
case of highly potent
compounds or a toxic).
2. Isolation - protect
the product from the
world (as in the case
of a sterile product).
3. ISO 14644-7 "Minienvironments
and Isolators"
will define further
levels of devices
Base
An electropositive
element or radical
that unites with an
acid to form a salt.
Or, a substance that
when dissolved in
water, dissociates
to produce one or
more hydroxyl ions
(OH-).
Base Pair
(bp)
Two nucleotides that
are in different nucleic
acid chains and whose
bases pair by hydrogen
bonding. In DNA, the
nucleotide bases are
adenine (A) that always
pairs with thymine
(T) and guanine (G)
which pairs with cytosine
(C). In RNA molecules,
adenine (A) joins
the uracil (U). Two
strands of DNA are
held together in the
shape of a double
helix by the bonds
between these pairs.
Base Sequence
The order of nucleotide
bases in a DNA molecule.
Base Sequence
Analysis A method,
sometimes automated,
for determining the
base sequence.
Baseline
In some analytical
procedures a sample
is dissolved in water
or combined with other
reagents for analysis.
A "blank"
or standard consisting
of the same reagents
may be analyzed without
sample present. This
provides a comparative
reference point, or
baseline, so that
the test results can
be attributed solely
to the sample itself.
Baseline®
Pharmaceutical Engineering
Guides (ISPE)
A series of industry
publications developed
in partnership with
the US Food and Drug
Administration (FDA).
Each volume in the
series is a collaborative
effort of industry
leaders representing
a broad cross-section
of manufacturers and
other industry experts.
The Guides document
current industry practice
for facilities and
systems used for production
of pharmaceutical
products and medical
devices. They are
intended to:
* Establish a baseline
approach to new and
renovated facility
design, construction,
commissioning, and
qualification that
is based upon clear
understanding of the
type of product and
its manufacturing
process.
* Prioritize facility
design features based
upon the impact on
product and process.
* Avoid unnecessary
spending on facility
features that do not
contribute to consistent
production of quality
products.
The Guides include
five product manufacturing
operation based guides
(vertical guides),
and three support
system/function based
guides (horizontal
guides):
1. Volume I - Bulk
Pharmaceutical Chemicals
(1996)
2. Volume II - Oral
Solid Dosage Forms
(1998)
3. Volume III - Sterile
Manufacturing Facilities
(1999)
4. Volume VI - Biotech
(in progress)
5. Volume -Oral Liquids
and Aerosols
6. Volume IV - Water
and Steam Systems
(in progress)
7. Volume V - Commissioning
and Qualification
Guide (in progress)
8. Volume VII - Packaging
and Warehousing
Basidiomycetes
Reproduce by basidiospores,
which are extended
from the stalks of
specialized cells
called the basidia.
The class comprises
Photobasidiomycetes
(smuts and rusts)
and the Hymenomycetes
(mushrooms and puffballs).
Basis of
Design
A design document
that describes what
the purpose of a given
system is and how
the system will accomplish
its required task.
This document is created
and approved before
the issuance of bid
specifications and
is often used to develop
them. Until the system
is developed this
is a conceptual document.
Batch
A specific quantity
of material produced
in a process or series
of processes so that
is expected to be
homogeneous within
specified limits.
In the case of continuous
production a batch
may correspond to
a defined fraction
of the production,
characterized by its
intended homogeneity.
The batch size may
be defined either
by fixed quantity
or the amount produced
in a fixed time interval.
Batch Number
A unique combination
of numbers and/or
letters which specifically
identify a batch or
lot and from which
the production and
distribution history
can be determined.
Batch Fermentation
The process in which
a fixed volume of
sterile medium in
a vessel is inoculated
with a desired organism.
The broth is fermented
for a defined period
to completion, without
further additions
of media. After discharging
the batch, the fermenter
is cleaned and rebatched
with medium for another
cycle. Two other types
of fermentation cycles
are fed batch and
continuous.
Batchwise Control
The use of validated
in-process sampling
and testing methods
such that results
prove the process
has done what it purports
to do for the specific
batch concerned, assuming
control parameters
have been appropriately
maintained.
Bed
Column of carbon,
sand, chromatography,
or ion exchange resins
through which a liquid
passes during operation.
Bed Depth
The height of the
exchange or capture
material in a column
after proper backwashing
for effective operation.
Bed Expansion
The effect produced
during backwashing;
resin particles separate
and rise in the column.
Regulating backwash
flow may control bed
expansion caused by
the increase in space
between resin particles.
Binary Explosive
An explosive material
composed of separate
components, each of
which is safe for
storage and transportation
and would not in itself
be considered as an
explosive.
Bioactivity
A protein's ability
to function correctly
after it has been
delivered to the active
site of the body (in
vivo).
Bioassay
The determination
of the biological
activity of a substance
(e.g. a drug) by observing
its effect on an organism
(or organ) compared
to a standard preparation.
Bioaugmentation
A strategy involved
in bioremediation
that increases the
activity of an organism
to break down or metabolize
a pollutant. This
involves reseeding
a waste site with
bacteria as they die.
Bioburden
The level and type
of microorganisms
which may be present
in raw materials,
API (Active Pharmaceutical
Ingredient) starting
materials, intermediates,
or APIs which have
defined limits and
should not affect
the quality of the
API. Bioburden should
not be considered
contamination unless
the levels have been
exceeded or defined
objectionable organisms
have been detected.
Biochemical
Oxygen Demand (BOD)
(also see: BOD (Biochemical
Oxygen Demand))
Biochemistry
The study of chemical
processes in living
things. Despite the
dramatic differences
in the appearance
of living things,
the basic chemistry
of all organisms is
strikingly similar.
Even tiny, one-celled
creatures carry out
essentially the same
reactions that each
cell of a complex
organism, such as
man, carries out.
Biocide
An agent that can
kill all pathogenic
and non-pathogenic
living organisms,
including spores.
More general than
bacteriocide, biocide
includes insecticides
and any compound toxic
to any living thing.
Biodegradable
Material that can
be broken down by
biological action.
Bioequivalency
A scientific basis
on which generic and
brand name drugs are
compared with one
another. Drugs are
bioequivalent if they
enter circulation
at the same rate when
given in similar doses
under similar conditions.
Biogenerator
A contained system,
such as a fermentor,
into which biological
agents are introduced
along with other materials
so as to effect their
multiplication or
their production of
other substances by
reaction with the
other materials. Biogenerators
are generally fitted
with devices for regulation,
control, connection,
material addition,
and material withdrawal.
Biohazard
An infectious agent(s),
or part thereof, presenting
a real or potential
risk to human, other
animals, or plants,
directly through infection
or indirectly through
disruption of the
environment.
Bioinformatics
The use of computers
in the life sciences,
electronic databases
of genomes and protein
sequences, and computer
modeling of biomolecules
and biologic systems.
Biologic
A therapeutic agent
derived from living
things.
Biological
Barrier
An impediment (naturally
occurring or introduced)
to the infectivity
and/or survival of
a microbiological
agent or eukaryotic
cell once it has been
released into the
environment.
Biological
Impurities
Impurities resulting
from living matter
(bacteria, virus,
algae, protozoa, microfungi)
and their by-products,
including pyrogens
(endotoxins).
Biological
Indicators
Resistant microorganisms
placed into or on
various materials
to confirm that a
sterilization process
is effective. They
may for instance be
placed within a filter
in order to determine
if a proposed autoclave
cycle is effective.
After autoclave, they
are removed and culture
tests are performed
to see if the microorganisms
were killed.
Biological
Oxygen Demand (BOD)
(also see: BOD (Biological
Oxygen Demand))
Biological
Reactivity Tests,
In Vivo
This classification
is based on responses
to a series of in
vivo tests for which
extracts, materials
and routes of administration
are specified. Six
Plastic Classes are
defined:
1. Class I - Uses
a specified dosage
of an extract of sample
in Sodium Chloride
Injection applied
either intravenously
or intracutaneously
into a mouse or a
rabbit.
2. Class II - Same
as Class I but in
addition uses an extract
of sample in 1 in
20 Solution of Alcohol
in Sodium Chloride
Injection applied
either intravenously
or intracutaneously
into a mouse or a
rabbit.
3. Class III - Same
as Class II but in
addition uses an extract
of sample in Polyethylene
Glycol 400, and an
extract of sample
in Vegetable Oil,
both applied either
intraperitoneally
or intracutaneously
into a mouse.
4. Class IV - Same
as Class II but in
addition uses an extract
of sample in Vegetable
Oil applied intraperitoneally
or intracutaneously
into a mouse or a
rabbit. Also uses
implant strips of
sample into a rabbit.
5. Class V - Same
as Class II but in
addition uses an extract
of sample in Polyethylene
Glycol 400, and an
extract of sample
in Vegetable Oil applied
intraperitoneally
or intracutaneously
into a mouse or a
rabbit.
6. Class VI - Same
as Class V but in
addition uses implant
strips of sample into
a rabbit.
These tests are
designed to determine
the biological response
of animals to elastomerics,
plastics and other
polymeric material
with direct or indirect
patient contact, or
by the injection of
specific extracts
prepared from the
material under test.
Three tests are described:
1. Systemic Injection
Test - Designed to
determine the systemic
biological responses
of animals to plastics
and other polymers
by the single-dose
injection of specific
extracts prepared
from a sample.
2. Intracutaneous
Test - Designed to
determine the local
biological responses
of animals to plastics
and other polymers
by the single-dose
injection of specific
extracts prepared
from a sample.
3. Implantation Test
- Designed to evaluate
the reaction of living
tissue to the plastic
and other polymers
by the implantation
of the sample (specimen
under test) itself
into animal tissue.
With the exception
of the Implantation
Test, the procedures
are based on the use
of extracts that,
depending on the heat
resistance of the
material, are prepared
at one of the three
standard temperatures:
50°, 70°, and 121°.
Therefore, the class
designation of a plastic
must be accompanied
by an indication of
the temperature of
extraction e.g., IV
- 121°, which represents
a class IV plastic
extracted at 121°).
Biological
Safety Cabinets (BSCs)
Bench-top or freestanding
cabinets with unidirectional
airflow used for handling
materials that present
a health hazard. The
National Institutes
of Health (NIH) Guidelines
classify them as:
1. Class I - A negative
pressure, ventilated
cabinet for personnel
protection having
an inward flow of
air away from the
operator. The exhaust
air is filtered through
a HEPA filter (located
at rear or top) either
into the laboratory
or to the outside.
This cabinet is designed
for general microbiological
research with low
and moderate risk
agents (BL-2 and BL-3
agents), and is used
in three operational
modes:
a) With a full width
open front. The face
velocity of the inward
flow of air through
the full width open
front is at least
75' feet per minute.
b) With an installed
front closure panel
(having four 6-inch
diameter openings)
without gloves. The
face velocity of the
inward flow of air
through the openings
will increase to approximately
150' feet per minute.
c) With an installed
front closure panel
equipped with arm-length
rubber gloves, and
inlet air pressure
relief for further
protection. In this
configuration, it
is necessary to install
a make-up air inlet
fitted with a HEPA
filter in the cabinet.
2. Class II - A
ventilated cabinet
for personnel and
product protection
having an open front
with inward airflow
for personnel protection
(75' to 100' feet
per minute), and HEPA
filtered downward
unidirectional airflow
for product protection.
The exhaust air is
filtered through a
HEPA filter for environmental
protection. For selection
and procurement of
Class II cabinets
refer to standards
developed by the National
Sanitation Foundation,
Ann Arbor, Michigan.
Cabinets are further
classified as:
a) Type A - Suitable
for microbiological
research in the absence
of volatile or toxic
chemicals and radionuclides
(BL-2 and BL-3), with
70% recirculated air
through HEPA. They
are exhausted through
HEPA into the laboratory
or to the outdoors
via a "thimble"
connection to the
building exhaust system.
b) Type B - Hard ducted
to the building exhaust
system, contains negative
pressure plena, and
face velocity of 100'
feet per minute. Type
B cabinets are further
sub-typed into types:
B1 (30% recirculated
air through HEPA;
exhaust via HEPA and
hard ducted. BL2 and
BL-3), B2 (No recirculation;
total exhaust via
HEPA and hard ducted.
BL-2 and BL-3), and
B3 (same as IIA, but
plena under negative
pressure to room and
exhaust air is ducted.
BL-2 and BL-3).
Classes I and II should
be located away from
traffic patterns and
doors, airflow from
fans, room air supply
louvers, and other
air moving devices.
3. Class III - Closed-front
ventilated cabinet
of gas tight construction
that provides the
highest level of personnel
protection from infectious
aerosols, as well
as protection of research
materials from microbiological
contaminants. The
interior of the cabinet
is protected from
contaminants exterior
to the cabinet. The
cabinet is fitted
with arm-length rubber
gloves and is operated
under negative pressure
of at least 0.5 inches
water gauge. All supply
air is filtered through
HEPA filters. Exhaust
air is filtered through
two HEPA filters in
series or one HEPA
filter and incinerator
before being discharged
to the outside environment.
Class III cabinets
are most suitable
for work with hazardous
agents that require
Biosafety Level 3
or 4 containment.
Cabinets must be connected
to a double-door autoclave
and/or chemical dunk
tank used to sterilize
or disinfect all materials
exiting the cabinet,
and to allow supplies
to enter the cabinet.
Biologics
"Any virus, therapeutic
serum, toxin, antitoxin,
vaccine, blood, blood
component or derivative,
allergenic product,
or analogous product…
applicable to the
prevention, treatment,
or cure of diseases
or injuries of man…"
Biomass
Organic matter
grown by the photosynthetic
conversion of solar
energy.
Biomass
The entire assemblage
of living organisms
(both plant and animal),
of a particular region,
considered collectively.
Biometabolism
Physical and chemical
processes that occur
within a cell or an
organism, for example,
the conversion of
nutrients into energy.
Biometrics
A method of verifying
an individual's identity
based on measurement
of his/her physical
feature(s) or repeatable
action(s) where those
features and/or actions
are both measurable
and unique to that
individual. The main
types of biometrics
are: face recognition,
finger scanning, hand
geometry, finger geometry,
iris recognition,
palm, retina, signature,
and voice recognition.
Bionics
An interscience discipline
for constructing artificial
systems, which resemble
or have the characteristics
of living systems.
Biopharmaceuticals
Ethical pharmaceutical
drugs derived through
bioprocessing.
Bioprocessing
The creation of a
product utilizing
a living organism.
Bioprocess
Engineering
Process that uses
complete living cells
or their components
(e.g., enzymes, chloroplast)
to effect desired
physical or chemical
changes.
Biopsy
The gross and microscopic
examination of tissues
or cells removed from
a living patient,
for the purpose of
diagnosis or prognosis
of disease, or for
the confirmation of
normal conditions.
Biopure Water
Water that is sterile,
pyrogen free and has
a total solids content
of less than 1 ppm.
Biosphere
All the living matter
on or in the earth,
the oceans and seas,
and the atmosphere.
Bioreactor
A closed system used
for bioprocessing
(flask, roller bottle,
tank, vessel, or other
container), which
supports the growth
of cells, mammalian
or bacterial, in a
culture medium. A
bacterial reaction
usually is said to
take place in a fermenter,
and cell culture in
a bioreactor.
Biosafety
Level
The National Institutes
of Health (NIH) specifies
physical containment
levels and defines
Biosafety Levels in
their "Guidelines
for Research Involving
Recombinant DNA Molecules"
- Appendix G - May
1999. There are four
biosafety levels for
operations performed
with infectious agents:
1. BL1: Practices,
safety equipment,
and facilities appropriate
for work performed
with defined and characterized
strains of viable
microorganisms not
known to cause disease
in healthy adult humans.
The Basic Laboratory.
This laboratory provides
general space in which
work is done with
viable agents that
are not associated
with disease in healthy
adults. Conventional
laboratory designs
are adequate. Areas
known to be source
of general contamination,
such as animal rooms
and waste staging
areas, should not
be adjacent to patient
care activities. Public
areas and general
offices to which non-laboratory
staff requires frequent
access should be separated
from spaces, that
primarily support
laboratory functions.
2. BL2: Practices,
safety equipment,
and facilities appropriate
for work performed
with a broad spectrum
of moderate risk agents
present and associated
with human disease
of varying severity.
The Basic Laboratory.
This laboratory provides
general space in which
work is done with
viable agents that
are not associated
with disease in healthy
adults. Conventional
laboratory designs
are adequate. Areas
known to be sources
of general contamination,
such as animal rooms
and waste staging
areas, should not
be adjacent to patient
care activities. Public
areas and general
offices to which non-laboratory
staff requires frequent
access should be separated
from spaces, which
primarily support
laboratory functions.
3. BL3: Practices,
safety equipment,
and facilities appropriate
for work performed
with indigenous or
exotic agents where
the potential for
infection by aerosols
is real and the disease
may have serious or
lethal consequences.
Just walking through
the area and breathing
the air could infect
one. The Containment
Laboratory. This laboratory
has special engineering
features that make
it possible for laboratory
workers to handle
hazardous materials
without endangering
themselves, the community,
or the environment.
The unique features
that distinguish this
laboratory from the
basic laboratory are
the provisions for
access control and
a specialized ventilation
system. The containment
laboratory may be
an entire building,
a single module, or
complex of modules
within a building.
In all cases, a controlled
access zone from areas
open to the public
separates the laboratory.
4. BL4: Practices,
safety equipment,
and facilities appropriate
for work performed
with dangerous and
exotic agents that
pose a high individual
risk of life-threatening
disease. Exposure
to the skin could
cause infection. The
Maximum Containment
Laboratory. This laboratory
has special engineering
and containment features
that allow activities
involving infectious
agents that are extremely
hazardous to the laboratory
worker or that may
cause serious epidemic
disease to be conducted
safely. Although the
maximum containment
laboratory is generally
a separate building,
it can be constructed
as an isolated area
within the building.
The laboratory's distinguishing
characteristic is
that it has secondary
barriers to prevent
hazardous materials
from escaping into
the environment. Such
barriers include sealed
openings into the
laboratory, airlocks
or liquid disinfectant
barriers, a clothing-change
and shower room contiguous
to the laboratory,
a double door autoclave,
a biowaste treatment
system, and a treatment
system to decontaminate
exhaust air.
(also see: Good
Large Scale Practice,
Containment Level,
and Table II, Section
II - Comparison of
Good Large Scale Practice
(GLSP) and Biosafety
Level (BL) - Large
Scale (LS) Practice)
Biosynthesis
The production, by
biological synthesis
or degradation, of
compounds by a living
organism (e.g. amino
acid synthesis, nucleotide
synthesis).
Biotechnology
An industry that creates,
develops, and markets
a variety of techniques
that use living organisms,
or substances from
those organisms, to
make or modify a product
by microbial and biochemical
processes. A common
misconception is that
biotechnology refers
only to recombinant
DNA or gene splicing
work. Recombinant
DNA is only one of
the many techniques
used to derive products
for organisms, plants,
and parts of both
for the biotechnology
industry. A list of
areas covered by the
term biotechnology
would more properly
include: plant tissue
culture, cell fusion
techniques (especially
for the production
of monoclonal antibodies),
enzyme systems, plant
breeding, meristem
culture, fermentation,
and others.
Biotechnology
A process of applying
genetic engineering
(recombinant DNA),
hybrid (monoclonal
antibody), hybridization
(gene probes), bioelectric,
etc. to commercial
applications in pharmaceutical,
chemical, medical
diagnostic device,
food, animal and plant
industries.
Biotechnology
Products Large molecules
that are not manufactured
by means of chemical
synthesis but rather
produced by means
of fermentation and/or
recovery, sourced
from genetically engineered
products.
Biowaste
Inactivation
The inactivation or
"killing"
of biological organisms
using heat or chemicals.
This step is done
at the end of the
processing to ensure
that there are no
living organisms remaining
in the effluent that
is sent to the sanitary
sewer system. Heat
is usually applied
at 130ºC (266ºF) for
mammalian cells. Chemicals
used include caustic
or acid.
BLA (Biologics
License Application)
The required application
for marketing a biologic
product in the United
States. Most biopharmaceuticals
are biologics.
Blank
A preliminary analysis
omitting only the
sample to provide
an unbiased reference
point or baseline
for comparison. It
is important to minimize
extraneous contamination
that could be confused
with constituents
in the sample itself.
Blind Weld
A "blind weld"
is defined as a pipe
or tube joint welded
automatically in which
there is no physical
way to inspect the
weld either visually
or with a borescope.
Blinding Clinical
trial technique in
which, to eliminate
bias in a research
study, subjects and/or
clinical investigators
remain unaware of
which investigational
product is provided.
Blood-Borne Pathogens
Infectious microorganisms
that are carried in
the blood of infected
humans or animals
and that can be transmitted
through contact with
infected blood, body
fluids, tissues, or
organs. Blood-borne
pathogens are implicated
in diseases such as
malaria, syphilis,
brucellosis, tuberculosis,
hepatitis B, and AIDS
(Acquired Immunodeficiency
Syndrome). Workplace
transmission of a
blood-borne pathogen
can occur via accidental
inoculation with a
contaminated "sharp"
exposure through open
cuts, skin abrasions,
and mucous membranes
of eyes and mouth
indirect transmission
(e.g., touching mouth,
eyes, nose or open
cuts with contaminated
hands).
Blood Corpuscle
A cell that circulates
in the blood.
Blood Plasma
Blood from which all
blood corpuscles,
with the exception
of platelet cells,
have been removed
(e.g. by centrifugation)
resulting in a clear,
straw-colored fluid,
which clots as easily
as whole blood.
Blood Platelets
Small, disc-shaped,
metabolically active
cells circulating
in the blood. They
are essential in the
blood clotting process
since they aggregate
to form a plug on
the injured surface
of the blood vessel.
Blood Serum
The liquid expressed
from clotted blood
or clotted blood plasma.
Blowdown
The bleeding-off of
fixed quantities of
accumulated feed water
to reduce concentrated
impurities. If these
impurities are permitted
to accumulate, they
may pass through the
distillation process
and contaminate the
distillate or foul
the distillation system.
Blowdown
The withdrawal of
water from an evaporating
water system to maintain
a solids balance within
specified limits of
concentration of those
solids.
Blow (Form)
Fill, Seal
Refers to machines
that combine formation
of a plastic container
by blow molding, aseptic
filling of a liquid
product and sealing
of the final package.
In the U.S., a major
company is ALP, or
Automatic Liquid Packaging
(Weiler Engineering)
and in Europe, Rommilog.
BME (Basic
Medium Eagles)
One of the most common
tissue culture media
composed of isotonic
salts, carbohydrates
and vitamins. When
combined with animal
serum. BME is a good
medium for cell proliferation.
BOD (Biochemical
Oxygen Demand)
The amount of oxygen
required to oxidize
the dissolved organic
matter in a water
sample by aerobic
(bacterial) decay.
A measure of the oxygen
depletion that would
result from discharging
organic impurities
into a waterway.
BOD (Biological
Oxygen Demand)
The oxygen used in
meeting the metabolic
needs of aerobic organisms
in water containing
organic compounds.
BPC (Bulk Pharmaceutical
Chemical)
A pharmaceutical product
derived by chemical
synthesis, in bulk
form, for later dispensing,
formulation or compounding,
and filling in a pharmaceutical
finishing facility.
Breakthrough Passage
of a substance through
a bed, filter, or
process designed to
eliminate it. For
ion exchange processes,
the first signs are
leakage of ions (in
mixed beds, usually
Silica) and the resultant
increase in conductivity.
For organic removal
beds, usually small,
volatile compounds
(Trihalomethanes (THMs)
are common in activated
carbon).
BSE (Bovine
Serum Albumin)
A blood protein that
makes up approximately
55-65% of the proteins
in the bovine serum.
Used as a size marker
on gels and as carrier
protein.
BSE (Bovine
Spongiform Encephalopathy)
Sometimes called "Mad
Cow Disease".
A disease of cattle
presumably caused
by a virus or other
unidentified entity
that affects the brain
and causes the cow
to behave erratically.
Prevalent in parts
of Europe but not
in the United States.
BSE is a contaminant
that is undesirable
in bovine sera. It
is not known whether
the causative agent
can be filtered out
since the causative
agent itself is not
known. In humans,
it is believed to
cause Creutzfeld-Jacob,
a disease affecting
the nervous system.
BVD (Bovine
Viral Diarrhea)
Viral contaminant
found in bovine sera.
Able to be filtered
out using 0.1 µm nylon
filters.
Bovine Of, relating
to, or from a cow:
such as Bovine Blood:
blood from a cow.
Braze Welding
A welding process
using nonferrous filler
metal that has a melting
point below that of
the base metals, but
above 427ºC (800ºF).
The filler metal is
not distributed in
the joint by capillary
attraction. This type
of welding has been
also called Bronze
welding, a misnomer.
Brazing
A metal joining process
wherein coalescence
is produced by use
of a nonferrous filler
metal having a melting
point above 427ºC
(800ºF), but lower
than that of the base
metals being joined.
The filler metal is
distributed between
the closely fitted
surfaces of the joint
by capillary action.
Breakthrough
The first appearance
in the effluent of
an ion-exchange unit
of unadsorbed components
similar to those that
deplete the activity
of the resin bed.
Breakthrough indicates
that the resin is
exhausted and needs
to be regenerated.
Breath Control
Shields
Typically made of
acrylic or plastic
materials, shields
protect product, equipment,
or the work from particulate
contamination expelled
by people.
Broad Spectrum
Over a wide range.
A broad-spectrum disinfectant
is effective against
a wide range of microorganisms
including bacterial
spores, mycobacteria,
non-lipid and lipid
viruses, fungi, and
vegetative bacteria.
Broth
The liquid culture
medium in which fermentation
or cell culture takes
place.
Btu (British
thermal unit)
The unit used to measure
the amount of heat
in a substance. One
Btu is the heat required
to produce a temperature
rise of 1°F. in one
lb. of water.
Bubble Point
Test
A filter leakage test
in which the filter
is wetted and air
pressure is applied
and slowly increased
until water is expelled
from the largest pores
and bubbles appear
from a submerged tube
in a downstream collection
vessel. Vigorous bubbling,
as opposed to a diffusional
airflow or occasional
bubbles, is indicative
of reaching the bubble
point. This visual
test can be fairly
accurate for low area
filters, such as discs.
When used to evaluate
high area filters,
it is subject to limitations
in observation, test
time, collection conditions,
and pressurization
rates. The bubble
point test is not
recommended for integrity
testing of filter
cartridges.
Buffer
A substance capable
of neutralizing both
acids and bases in
solution, thereby
maintaining the original
acidity or causticity
of the solution.
Buffer Prep
Area Section of most
biotech facilities
devoted to the preparation
of controlled bioburden
buffer solutions for
use in the chromatographic
separation area of
those facilities.
Building
Occupancy Classification
(California Building
Code)
Every building, whether
existing or to be
erected, is classified
by the building official
according to its use
or the character of
its occupancy. The
occupancy groups are
as follows:
1. Group A - Assembly
(Section 303.1.1)
2. Group B - Business
(Section 304.1)
3. Group C - Organized
Camp (Section 431A)
4. Group E - Educational
(Section 305.1)
5. Group F - Factory
and Industrial (Section
306.1)
6. Group H - Hazardous
(Section 307.1) (also
see: Hazardous Occupancy
- Group H)
7. Group I - Institutional
(Section 308.1)
8. Group M - Mercantile
(Section 309.1)
9. Group R - Residential
(Section 310.1)
10. Group S - Storage
(Section 311.1)
11. Group U - Utility
(Section 312.1)
Bulk Handling
The transferring of
flammable or combustible
liquids from tanks
or drums into smaller
containers for distribution.
Bulk Oxygen
System
An assembly of equipment,
such as storage containers,
pressure regulators,
safety devices, vaporizers,
manifolds, and interconnecting
piping that has a
storage capacity of
more than 12,000 cubic
feet (340 m³) of oxygen
at normal temperature
and pressure, connected
in service or ready
for service, or more
than 25,000 cubic
feet (708 m³) of oxygen,
including unconnected
reserve on hand at
the site.
Bulk Pharmaceutical
Chemical (BPC)
(also see: BPC (Bulk
Pharmaceutical Chemical))
Byte
An abbreviation for
binary term. A storage
unit capable of holding
eight bits or the
space required for
a single letter or
number, a single character.
C
Calcium
A metallic dyad element
of a lustrous yellow
color, symbol Ca,
atomic number 20,
atomic weight 40.09,
melting point 810°,
often found in water
usually as dissolved
calcium carbonate,
chalk (CaCO3). Soluble
in water, it causes
hardness and subsequent
scaling.
Calcium Carbonate
Equivalent
The value obtained
when salts are calculated
in terms of equivalent
quantities of calcium
carbonate. This is
a convenient method
of reducing all salts
to a common basis
for comparison.
ppm CaCO3 = ppm ion
X
Equivalent weight
of CaCO3
-------------------------------------
Equivalent weight
of ion
Where ion = magnesium,
calcium, or other
elements that contribute
to hardness.
Calibration
A comparison of a
measurement standard
or instrument of unknown
accuracy to detect,
correlate, report,
or eliminate by adjustment
of any variation in
the accuracy of the
unknown standard or
instrument.
Calibration
(ICH API defintion)
The demonstration
that a particular
instrument or device
produces results within
specified limits by
comparison with those
produced by a reference
or traceable standard
over an appropriate
range of measurements.
Calorie
Any of several approximately
equal units of heat,
each measured as the
quantity of heat required
to raise the temperature
of one (1) gram of
water by °C from a
standard initial temperature,
specially from 3.98°C,
14.5°C, or 19.5°C,
at a constant pressure
of one (1) atmosphere.
Also called "gram
calorie", "small
calorie".
The unit of heat equal
to 1/100 the quantity
of heat required to
raise the temperature
of one (1) gram of
water from 0°C to
100°C at one (10 atmosphere
pressure. Also called
"mean calorie".
The unit required
to raise the temperature
of one (1) Kilogram
of water by 1°C at
one (1) atmosphere
pressure. Also called
"kilogram calorie",
"large calorie".
Calorimetry
Analytical method
that measures heat
loss or gain resulting
from physical or chemical
changes in a sample.
Differential scanning
calorimetry compares
the results of heating
a sample to those
for heating a reference
material. For example,
a method to measure
the temperature at
which the sample crystallizes,
changes phases, or
decomposes.
Cancer
The name given to
a group of diseases
that are characterized
by uncontrolled cellular
growth.
Capsid
The external protein
shell or coat of a
virus particle.
Carbohydrates
A large class of carbon-hydrogen-oxygen
compounds that includes
the sugars and their
polymers (mainly starch,
glycogen and cellulose).
Most carbohydrates
are produced by photosynthesis
in plants. They are
the major food compounds
for both plants and
animals. One group
of carbohydrates,
cellulose, is the
primary structural
material of plants.
Carbon Filter
A vessel loaded with
activated carbon and
used to remove organics,
chlorine, tastes,
and odors from liquids,
operating on the principle
of adsorption.
Carbon Thickness
A measurement of surface
organic material.
Carbon thickness values
typically range from
5 to 20 angstroms
(Å). Significantly
contaminated surfaces
can show surface carbon
thickness of 20 angstroms
(Å) or more.
Carbonate
Hardness
That hardness in water
caused by bicarbonates
and carbonates of
calcium and magnesium.
If alkalinity exceeds
total hardness, all
hardness is carbonate
hardness; if hardness
exceeds alkalinity,
the carbonate hardness
equals the alkalinity.
Carcinogen
A substance that causes
the development of
cancerous growths
in living tissue.
A chemical is considered
to be a carcinogen
if it has been evaluated
by the International
Agency for Cancer
Research (IARC) and
found to be a carcinogen
or potential carcinogen,
or if it is listed
in the Annual Report
on Carcinogens published
by the National Toxicology
Program, or if it
is regulated by OSHA
as a carcinogen.
Carcinogenic
Cancer-causing. Many
agents that are carcinogenic
are mutagens.
Carrier
A person who has a
recessive mutated
gene, together with
its normal allele.
Carriers do not usually
develop disease but
can pass the mutated
gene on to their children.
Catabolism
The intracellular
phase of metabolism
involved in the energy-yielding
degradation of nutrient
molecules (for example,
glucose to CO2 and
H2O). Waste products
are called catabolites.
Catalase
An enzyme that catalyzes
the decomposition
of hydrogen peroxide
and molecular oxygen
and water.
Catalyst
A compound that increases
the rate of a chemical
reaction without being
consumed or changed.
In the biosciences,
the term enzyme is
used. Enzymes catalyze
biological reactions.
Cation
A positively charged
particle or ion.
Cation Exchange
The displacement of
one positively charged
particle by another
on a cation-exchange
material.
Cation Exchange
Resin
An Ion exchange resin,
which removes positively
charged ions (cations)
by exchanging them
for hydrogen ions.
Cavitation
A condition of liquid
flow where, after
partial vaporization
of the liquid, the
subsequent collapse
of vapor bubbles can
produce surface damage.
CBER
(also see: center
for Biologics Evaluation
and Research)
Center For
Biologics Evaluation
and Research (CBER)
The FDA successor
to the Bureau of Biologics
concerned with biologic
drugs, and most importantly,
with the new protein
and peptide drugs
emanating from biotechnology.
Center For
Drug Evaluation and
Research (CDER)
The successor to the
Bureau of Drugs of
the FDA concerned
with all SVPs (Small
Volume Parenterals),
LVPs (Large Volume
Parenterals), and
non-biological drugs.
Certified
Vendor Drawings
Drawings prepared
by vendors for the
fabrication of equipment,
specialty components
and skid mounted systems.
These are certified
as fabricated by the
vendor and become
the official document
for the equipment
involved.
Celsius
Of or pertaining to
a temperature scale
that registers the
freezing point of
water as 0°C and the
boiling point as 100°C
under normal atmospheric
pressure. Also called
"centigrade".
The designation Celsius
has been official
since 1948, but centigrade
remains in common
use.
Cell
The fundamental unit
of life. The living
tissue of almost every
organism is composed
of these fundamental
living units. Unicellular
organisms, such as
yeast or a bacterium,
perform all life functions
within the one cell.
In a higher organism,
a multicellular organism,
entire populations
of cells may be designated
a particular task.
The cells of muscle
tissue, for example,
are specialized for
movement.
Cell Bank
Master Cell Bank:
The bank of cells,
which contain the
original unused mutated
cells from which,
the Manufacturing
Working Cell Bank
is taken. This is
usually kept under
lock with very limited
access.
Manufacturing Working
Cell Bank: The bank
of cells derived from
the Master Cell Bank,
which are used to
seed the fermentation
manufacturing process.
Cell Culture
The in vitro propagation
of cells removed from
organisms in a laboratory
environment that has
strict sterility,
temperature, and nutrient
requirement; also
used to refer to any
particular individual
sample. Usually, cell
culture takes place
in a bioreactor.
Cell Differentiation
The process whereby
descendants of a common
parental cell achieve
and maintain specialization
of structure and function.
Muscle cells become
muscle cells and bone
cells develop. In
humans all the different
types of cells differentiate
from the simple sperm
and egg.
Cell Fusion
The fusing together
of two or more cells
to become a single
cell. This technique
has had important
consequences in immunology,
developmental biology,
and genetics. For
example, monoclonal
antibodies are produced
by fusing a spleen
cell (producing an
antibody specific
for the antigen of
interest) with a mouse
myeloma cell to produce
a hybridoma which
has an indefinitely
long life because
of the myeloma component
and which secretes
a specific antibody.
When a human cell
is fused with a mouse
cell, the human chromosomes
are progressively
lost from the resultant
hybrid and by correlating
the presence of proteins
in the hybrid with
the presence of particular
human chromosomes,
genes can be assigned
to individual chromosomes.
Cell Lines
When cells from the
first culture (taken
from the organism)
are used to make subsequent
cultures, a cell line
is established. "Immortal"
cell lines can replicate
indefinitely.
Cellulose
A polymer of six-carbon
sugars found in all
plant matter, the
most abundant biological
compound on earth.
Centimorgan
(cM)
A unit of measure
of recombination frequency.
One centimorgan is
equal to a 1% chance
that a marker at one
genetic locus will
be separated from
a marker at a second
locus due to crossing
over in a single generation.
In human beings, one
centimorgan is equivalent,
on average, to one
million base pairs.
Centrifugation
Mechanical means of
separation based on
differences in sedimentation
rates due to differences
in density between
the suspended particles
in the liquid.
Centrifuge
A centrifuge operates
on the principle of
centrifugal force,
the inertial reaction
by which a body tends
to move away from
a center about which
it revolves. This
technique is commonly
used to separate solids
from liquids or liquids
of different densities.
Centrifugal equipment
is divided into two
major types, sedimenters
and filters:
Sedimenters
For sedimentation,
batch and continuous
centrifuges are available.
There are three types
of centrifuges for
continuous sedimentation.
a) Disc - constructed
on the vertical axis,
disc centrifuges are
solid-bowl units.
All are capable of
separating liquids
from solids, solids
from two immiscible
liquids and two immiscible
liquids. Disc-stack
centrifuges differ
in their ability to
handle different volumes
of solids in the feed
stream, and in the
way that the separated
solids are removed
from the separation
vessel: solids-retaining,
solids-ejecting, and
nozzle-bowl separators.
b) Decanters - consists
of a cylindrical settling
section with a tapered
end. Inside the bowl
is a scroll conveyor
that is driven usually
at a slightly faster
rate than the bowl
and can be controlled
by a differential
speed device or back
drive.
c) Tubular - a vertical
solid-wall cylinder
provided with caps
on both ends; a tubular
centrifuge generally
has a bottom feed
inlet. When two liquids
of different specific
gravities are fed,
the heavier phase
is concentrated against
the wall, while the
lighter phase "floats"
on the heavier phase.
Filters
Filtering centrifuges
accommodate a range
of liquid-solid separations.
The two batch types,
basket and peeler
centrifuges, can separate
almost any liquid-solid
slurry. For continuous
operation, there are
pusher and conical
centrifuges.
a) Pusher - with
a horizontal axis,
the pusher centrifuge
operates at a constant
fixed speed. It has
a perforated bowl,
generally with a bar-type
screen. One end of
the bowl is open while
the opposite end is
closed with a reciprocating
diaphragm, or disc,
which rotates with
the bowl.
b) Conical - the standard
conical centrifuge
consists of a cone
with a small closed
end and a large open
end to which is attached
a coarsely woven drainage
screen, topped with
a filter screen or
perforated plate.
A compartmentalized
casing surrounds the
bowl. There are two
variations of the
basic conical centrifuge:
the tilting conical
centrifuge and the
conveyor conical type.
Centromere
A specialized chromosome
region to which mitotic
or meiotic spindle
fibers attach during
cell division.
Certification
Documented testimony
by qualified authorities
that a system qualification,
calibration, validation,
or revalidation has
been performed appropriately
and that the results
are acceptable. Personnel
certification is proof
that a person has
achieved a certain
level of qualification.
CFR
(Code of Federal regulations)
Title 21
The U.S. regulations
that directly apply
to biopharmaceutical
development are contained
in Title 21 parts
58 (Good Laboratory
Practice for Nonclinical
Laboratory Studies),
210 (Current Good
Manufacturing Practice
in Manufacturing,
Processing, Packing,
or Holding of Drugs;
General), 211 (Current
Good Manufacturing
Practice for Finished
Pharmaceuticals),
and 600 (Biological
Products: General).
Parts 50 (Protection
of Human Subjects),
56 (Institutional
Review Boards), and
312 (Investigational
New Drugs) apply to
critical trials.
Part 11 provides criteria
which will consider
electronic records
to be equivalent to
paper records and
electronic signatures
to be equivalent to
traditional handwritten
signatures. (also
see: cGMPs (current
Good Manufacturing
Practices))
CFU
(Colony Forming Unit)
A measure of the number
of bacteria present
in the environment
or on the surfaces
of an aseptic processing
room, measured as
part of qualification
and ongoing monitoring.
Also applied to the
testing of purified
water samples.
cGMPs
(current Good Manufacturing
Practices)
Current accepted standards
of design, operation,
practice, and sanitization.
The FDA is empowered
to inspect drug-manufacturing
plants in which drugs
are processed, manufactured,
packaged, and stored
for compliance with
these standards.
Change Control
A formal system by
which qualified representatives
of appropriate disciplines
review proposed or
actual changes that
might affect a validated
process's status.
The intent is to determine
the need for action
that would ensure
that the system is
maintained in a validated
state.
Change Over
The program by which
a processing area
is cleared of supplies
and components used
in the manufacture
of a previous product
and then readied for
production of a new
product. This often
includes parts change
over and/or special
cleaning to eliminate
cross-contamination.
Channeling
Cleavage, cracking,
and furrowing of a
resin bed due to resin
age, a change in one
of the feed solutions,
or faulty operational
procedures. The solution
being treated follows
the path of least
resistance, runs through
these furrows, and
fails to contact active
resin material in
other parts of the
bed.
Characterization
Precisely deciphering
and describing all
the characteristics
of a drug substance
that affect its efficacy
and its purity. Or
the chemical, physical,
and sometimes biological
properties that are
attributes of a specific
drug substance.
Checksum
A record of the number
of bits transmitted
and included with
the transmission so
that the receiving
program can check
to see whether the
same number of bits
arrived. If the counts
match, it is assumed
that the complete
transmission was received.
Chelating
Agents
Organic compounds
that can withdraw
ions from solution,
forming insoluble
complexes.
Chemoautotrophs
Facultative autotrophs
that obtain their
energy from the oxidation
of inorganic compounds.
Chemostat
A growth chamber that
keeps a bacterial
culture at a specific
volume and rate of
growth by limiting
nutrient medium and
removing spent culture.
Chemotherapy
Treatment of disease
by means of chemical
substances or drugs.
Chimeric
An organism, especially
a plant, containing
tissues from at least
two genetically distinct
parents. Type of antibody,
partially human and
partially mouse.
Chloramine
A chlorine compound
formed by reaction
with organic amines
or ammonia.
Chlorinated
Vinyls
Thermoplastic chlorinated
vinyls include PVC,
CPVC, and VDC. PVC
and CPVC are very
similar materials,
the primary difference
being the addition
of more chlorine to
the PVC molecule to
synthesize CPVC. This
results in a higher
glass transition temperature
that equates to a
higher use temperature
for CPVC. The polymerization
with chlorine also
makes these materials
inherently flame resistant.
In addition to being
resistant to higher
temperatures, CPVC
is more resistant
to process chemicals.
Chlorination
Adding chlorine or
chlorine compounds
to water for disinfection.
Chlorine
An element used to
kill microorganisms
in water. At room
temperature and atmospheric
pressure a greenish
yellow gas.
Chlorine
Demand
Amount of chlorine
used up by reacting
with oxidizable substances
in water before chlorine
residual can be measured.
Chlorine
Residual
Portion of free or
combined chlorine
that remains active
after specified contact
period.
Chloroplasts
Relatively large,
chlorophyll containing,
green organelles responsible
for photosynthesis
in photosynthetic
eukaryotes, such as
algae and plant cells.
Every chloroplast
contains an outer
membrane and a large
number of inner membranes
called thylakoids.
CHO (Chinese
Hamster Ovary) Cells
In cell culture, the
cells of a female
hamster's reproductive
organs, which historically
have proven to be
excellent expression
systems in analytical
studies and for producing
pharmaceutical proteins.
Chromatids
Copies of a chromosome
produced by replication.
Chromatin
The complex of DNA
and protein in the
nucleus of the interphase
cell, originally recognized
by its reaction with
stains specific for
DNA.
Chromatography
Procedure by which
solutes (e.g., proteins
and other chemical
products) are selectively
separated by a dynamic
differential migration
process in a system
consisting of two
or more phases, one
of which moves continuously
in a given direction
and in which the individual
substances exhibit
different mobilities
by reason of differences
in adsorption, partition,
solubility, vapor
pressure, molecular
size, or ionic charge
density. The individual
substances thus obtained
can be identified
or determined by analytical
methods. There are
several types of chromatography
in use with different
operating principles:
1. Adsorption -
separates products
by their different
affinities for the
surface of a solid
medium, either an
inorganic carrier
such as silica gel,
alumina, or hydroxyapatite,
or an organic polymer.
2. Ion Exchange -
uses ion exchange
resin to which ionized
functional groups
have been attached.
At an appropriate
pH, target proteins
acquire a net surface
charge that allows
them to selectively
bind to an ion exchange
resin. Other impurities
are eluted through
the column.
3. Gel Filtration
- employs a neutral
cross-linked carrier
with a defined pore
size for molecular
fractionation. Molecules
larger than the largest
pores cannot enter
the matrix and pass
directly through the
column; smaller molecules
enter the carrier
and are retarded.
Gel filtration thus
separates on the basis
of molecular size,
eluting larger molecules
first, followed by
progressively smaller
species.
4. Affinity - relies
on the propensity
of each biomolecule
to have an affinity
for another highly
specific biomolecule,
such as an antibody-antigen
relationship. Once
bound together, the
drug molecules can
be detached by altering
various chemical attributes
in the column.
5. Hydrophobic - separates
by molecule polarity
and reverse interaction
with water.
6. High Pressure Liquid
Chromatography (HPLC)-
Chromium
Enrichment Layer Thickness
In stainless steel,
the same as its maximum
depth of enrichment,
unless a surface iron
layer is present in
which case the chromium
enrichment layer is
calculated as the
maximum depth of enrichment
minus the thickness
of the surface iron
oxide layer.
Chromosome
The self-replicating
genetic structure
of cells containing
the cellular DNA that
bears in its nucleotide
sequence the linear
array of genes. In
prokaryotes, chromosomal
DNA is circular, and
the entire genome
is carried on one
chromosome. Eukaryotic
genomes consist of
a number of chromosomes
whose DNA is associated
with different kind
of proteins.
CIP (Clean
In Place)
Internally cleaning
a piece of equipment
without relocation
or disassembly. The
equipment is cleaned
but not necessarily
sterilized. The cleaning
is normally done by
acid, caustic, or
a combination of both,
with WFI rinse. The
design of a CIP system
should considered
the operating volume
design for the water
consumption, chemical
and biowaste effluent,
and energy required
to clean a given circuit
or piece of equipment.
Class 100
Classification of
an aseptic processing
area where particle
count should not exceed
100 particles (3,530
particles per cubic
meter) 0.5µm or larger,
per cubic foot of
air, and no more than
0.1 CFU (Colony Forming
Units) per cubic foot.
Target uniform air
velocity is 90 fpm
plus or minus 20%,
HEPA filtered air.
(also see Table I,
Section II - Comparison
of Airborne Particulate
Cleanliness Classes)
Class 1,000
Classification of
an area where particle
count should not exceed
1,000 particles (35,300
particles per cubic
meter) 0.5µm or larger,
per cubic foot of
air. Supplied by HEPA
filtered air. Class
1,000 is not a pharmaceutical
GMP expectation. (also
see Table I, Section
II - Comparison of
Airborne Particulate
Cleanliness Classes)
Class 10,000
Classification of
an area where particle
count should not exceed
10,000 particles (353,000
particles per cubic
meter) 0.5µm or larger,
per cubic foot of
air. Minimum of 20
air changes per hour,
HEPA filtered air.
(also see Table I,
Section II - Comparison
of Airborne Particulate
Cleanliness Classes)
Class 100,000
Classification of
an area where particle
count should not exceed
100,000 particles
(3,530,000 particles
per cubic meter) 0.5µm
or larger, per cubic
foot of air, and no
more than 2.5 CFU
(Colony Forming Units)
per cubic foot. Minimum
of 20 air changes
per hour of HEPA filtered
air. (also see Table
I, Section II - Comparison
of Airborne Particulate
Cleanliness Classes)
Class Name
"For naming and
describing the classes,
SI names and units
are preferred; however,
English (U.S. customary)
units may be used".
Federal Standard 209E
superseded by ISO
14644-1). (also see
Table I, Section II
- Comparison of Airborne
Particulate Cleanliness
Classes)
Class 95%
ASHRAE Area
This area designation
refers to the efficiency
of the filters based
on ASHRAE standard
52-76. These areas
would have 95% efficient
supply air filtration,
unlike classified
areas, which would
have HEPA filtration.
This classification
is not specified in
Federal Standard 209E
or ISO 14644-1.
Class 65%
ASHRAE Area
This area would have
65% efficient filtration.
This classification
is not specified in
Federal Standard 209E
or ISO 14644-1.
Class 30%
ASHRAE Area
This area would have
30% efficient filtration.
This classification
is not specified in
Federal Standard 209E
or ISO 14644-1.
Classical
Pharmaceuticals
Small-molecule, nonbiotech
drugs produced by
chemical synthesis.
Classification
The level (or the
process of specifying
or determining the
level) of airborne
particulate cleanliness
applicable to a cleanroom
or clean zone, expressed
in terms of an ISO
Class N, which represents
maximum allowable
concentrations (in
particles per cubic
meter of air) for
considered sizes of
particles. ISO 14644-1
(also see Table I,
Section II - Comparison
of Airborne Particulate
Cleanliness Classes)
Classified
Space
A space in which the
number of airborne
particles is limited.
This is accomplished
by the strict use
of HVAC systems. Areas
are classified as
Class 10, Class 100,
Class 1,000, Class
10,000, and Class
100,000. In pharmaceutical
production, only classes
100, 10,000, and 100,000
are used. (also see
Table I, Section II
- Comparison of Airborne
Particulate Cleanliness
Classes)
Clean Air
Device
Stand-alone equipment
for treating and distributing
clean air to achieve
defined environmental
conditions.
Clean Air
Projector
Fan and filter unit
used to locally clean
room air and deliver
it to a desired location.
Often called a fan/filter
unit.
Clean Area
An area where particulate
and microbial levels
are specified (e.g.,
Filling Room - Class
10,000 "In Operation")
Clean In
Place (CIP)
(also see: CIP (Clean
In Place))
Cleanroom
A specially constructed
space environmentally
controlled with respect
to airborne particles
(size and count),
temperature, humidity,
air pressure, airflow
patterns, air motion,
and lighting. ISO
14644-1 defines it
as "a room in
which the concentration
of airborne particles
is controlled, and
which is constructed
and used in a manner
to minimize the introduction,
generation, and retention
of particles inside
the room, and in which
other relevant parameters,
e.g. temperature,
humidity, and pressure,
are controlled as
necessary." (also
see Table I, Section
II - Comparison of
Airborne Particulate
Cleanliness Classes)
Cleanroom
Classification
The maximum number
of particles greater
than or equal to 0.5µm
in diameter that may
be present in a cubic
foot of room air.
Clean Space
A room or volume controlled
to meet a certain
airborne particulate
limit (Class or Grade).
In pharmaceutical
facilities, clean
spaces are usually
classified and controlled
only for aseptic processing
facilities, but may
also be defined for
certain biotech processes.
Final non-sterile
bulk facilities, oral
product, most topical
product manufacturing
facilities, and warehouses
are normally not classified
as clean spaces.
Clean Steam
Steam free from boiler
additives that may
be purified, filtered,
or separated. When
condensed, clean steam
meets the specification
for WFI. Usually utilized
to sterilize process
equipment.
Clean Zone
ISO 14644-1 defines
it as "a dedicated
space in which the
concentration of airborne
particles is controlled,
and which is constructed
and used in a manner
to minimize the introduction,
generation, and retention
of particles inside
the zone and in which
other relevant parameters,
e.g. temperature,
humidity, and pressure,
are controlled as
necessary". Additionally,
ISO 14644-1 states,
"this zone may
be open or enclosed
and may or may not
be located within
a cleanroom".
Cleavage
The splitting up of
a complex molecule
into two or more simpler
molecules. The series
of cell divisions
occurring in the ovum
immediately following
its fertilization.
Clinical
Endpoint
An indicator (such
as blood pressure)
measured in a human
subject to asses the
safety, efficacy,
or other objective
of a clinical trial.
Clinical
Hold
The temporary cessation
of a clinical trial
by FDA if the agency
is concerned about
a drug or study protocol.
The trial may resume
when the problem is
solved.
Clinical
Trials
Testing of INDs (Investigational
New Drugs) in human
subjects to prove
safety and efficacy
prior to the drug's
approval for marketing.
The investigation
of a previously untested
drug is generally
divided into three
phases:
1. Phase I: Introducing
the product (or drug)
into a small number,
generally 20 to 80,
patients or healthy
volunteers to determine
the drug's metabolism,
pharmacological actions,
and side effects associated
with increasing doses.
2. Phase II: introducing
the product (or drug)
into a small number,
generally no more
than several hundred,
patients with the
disease or condition
under study to evaluate
the effectiveness
of the drug, common
short-term side effects
and risks associated
with its use.
3. Phase III: Introducing
the product (or drug)
into several hundred
to several thousand
subjects. Studies
are expanded controlled
and uncontrolled trials
performed after preliminary
evidence suggesting
effectiveness of the
drug has been obtained.
If the results of
the Phase III Clinical
Trials are favorable,
then the FDA will
normally license the
drug for manufacture
and sale. This phase
is usually performed
using double blind
studies with a placebo
and the actual drug.
4. Phase IV: Ongoing
testing studies conducted
after the drug is
approved. This is
done to ensure the
long-term efficacy
of the drug, detect
any long-term beneficial
and/or detrimental
side effects, and
to determine additional
potential uses for
the drug
Clone
A population of genetically
identical cells derived
from the multiplication
of a single cell.
It is the basis of
rDNA and monoclonal
antibody production.
Clone
A group of individuals
produced from one
individual through
asexual processes
that do not involve
the interchange or
combination of genetic
material. As a result,
members of a clone
have identical genetic
compositions. Protozoa
and bacteria, for
example, frequently
reproduce asexually
by a process called
binary fission. In
binary fission, a
single-celled organism
undergoes cell division
and the result is
two cells with identical
genetic composition.
Next, these two identical
cells undergo division
and the result is
four cells with identical
genetic composition.
These identical offspring
are all members of
a clone.
Cloning
Using specialized
DNA technology (also
see: Cloning Vector)
to produce multiple,
exact copies of a
single gene or other
segment of DNA to
obtain enough material
for further study.
This process is used
by researchers in
the Human Genome Project,
and is referred to
as cloning DNA. The
resulting cloned (copied)
collections of DNA
molecules are called
clone libraries. A
second type of cloning
exploits the natural
process of cell division
to make many copies
of an entire cell.
The genetic makeup
of these cloned cells,
called a cell line,
is identical to the
original cell. A third
type of cloning produces
complete, genetically
identical animals
such as the famous
Scottish sheep, Dolly.
Cloning Vector
DNA molecule originating
from a virus, a plasmid,
or the cell of a higher
organism into which
another DNA fragment
of appropriate size
can be integrated
without loss of the
vectors capacity for
self-replication;
vectors introduce
foreign DNA into host
cells, where it can
be reproduced in large
quantities. Examples
are plasmids, cosmids,
and yeast artificial
chromosomes; vectors
are often recombinant
molecules containing
DNA sequences from
several sources.
Closed System
One in which by its
design and proper
operation, prevents
release of a microbiological
agent or eukaryotic
cell contained therein.
Closed System
System sterilized-in-place
or sterilized while
closed prior to use,
is pressure or vacuum
tight to some predefined
leak rate, can be
utilized for its intended
purpose without breach
to the integrity of
the system, can be
adapted for fluid
transfers in or out
while maintaining
asepsis, and is connectable
to other closed systems
while maintaining
integrity of all closed
systems. (From PDA
TR-28 for sterile
product manufacture)
Clostridium
A genus of bacteria,
most are obligate
anaerobes and form
endospores.
cM
(also see: Centimorgan)
Coagulation
Adding insoluble compounds
to water to neutralize
the electrical charge
on colloids, causing
them to coalesce to
form larger particles
that can be removed
by settling.
Coaguligand
A VTA (Vascular Targeting
Agent) that utilizes
a human coagulation
protein to induce
tumor blood vessel
clotting.
Coccus
A bacterium of round,
spheroidal, or ovoid
form, including micrococcus,
staphylococcus, streptococcus,
and pneumococcus.
COD (Chemical
Oxygen Demand)
The amount of oxygen
needed to completely
oxidize all oxidizable
organic and inorganic
substances in water.
Coding Sequence
The region of a gene
(DNA) that encodes
the amino acid sequence
of a protein.
Coenzyme
A non-polypeptide
molecule required
for the action of
certain enzymes; often
contains a vitamin
as a component.
Cofactor
Small molecular weight,
heat stable inorganic
or organic substance
required for the action
of an enzyme.
Coliform
Bacteria
A group of bacteria
found in mammalian
intestines and soil,
used as a measure
of fecal pollution
in water. They are
easy to identify and
count in the laboratory
because of their ability
to ferment lactose.
Colonoscopy
Examination of the
colon through a flexible,
lighted instrument
called a colonoscope.
Colony
A growth of microorganisms
on a solid medium.
The growth is visible
without magnification.
Collagen
An albuminoid present
in connective tissue,
bone (ossein), and
cartilage (chondrin),
notable for its high
content of the imino
acids proline and
hydroproxilone. On
boiling with water
it is converted into
gelatin.
Collateral
Targeting
The therapeutic strategy
of targeting structures
and cell types other
than cancer cells
common to all solid
tumors as a means
to attack a solid
tumor.
Colloid
A translucent, yellowish
material of the consistency
of glue, less fluid
than mucoid or mucinoid,
found in the cells
and tissues in a state
of colloid degeneration
or colloid carcinoma.
A substance, such
as gelatin or cytoplasm
that because of the
size of its molecules,
is slowly diffusible
rather than soluble
in water and is incapable
of passing through
an animal membrane.
Colloids
Particles so fine
they will not settle
without prior coagulation.
They range from 10
Å to 1,000 Å (Angstroms).
They have a net negative
charge and readily
clog membranes and
foul resin beds. Examples
are bacteria, silica,
and clay.
CMC (Chemistry,
Manufacturing, and
Controls)
The section on a BLA
(Biologics License
Application) or IND
(Investigational New
Drug) describing the
composition, manufacture,
and specifications
of a drug product
and its ingredients.
Combustible
Dust
Any finely divided
solid material that
is 420µ or 0.017 inches
or less in diameter,
or any material capable
of passing through
an US No. 40 standard
sieve that when dispersed
in air in the proper
proportions, could
be ignited by a flame,
spark or other source
of ignition.
Combustible
Liquid
A liquid having a
closed cup flash point
at or above 100°F
(37.8°C). Combustible
liquids do not include
compressed gases or
cryogenic fluids.
Combustible liquids
are subdivided as
follows:
1. Class II - Liquids
having a closed cup
flash point at or
above 100°F (37.8°C)
and below 140°F (60°C)
2. Class III-A - liquids
having a closed cup
flash point at or
above 140°F (60°C)
and below 200°F (93.3°C)
Class III-B - liquids
having a closed cup
flash point at or
above 200°F (93.3°C).
Commissioning
A prescribed number
of activities designed
to take equipment
and systems from static,
substantially complete
state to an operable
state.
Commissioning
The documented process,
verifying that equipment
and systems are installed
according to specifications,
placing the equipment
and systems into active
service and verifying
its proper operation.
Commissioning is done
for good business,
but can include many
Qualification activities.
Complementary
DNA (cDNA)
DNA that is synthesized
from a messenger RNA
template; the single-stranded
form is often used
as a probe in physical
mapping.
Complementary
Sequence
Nucleic acid base
sequence that can
form a doublestranded
structure by matching
base pairs with another
sequence; the complementary
sequence to GTAC is
CATG.
Compounding
The bringing together
of excipient and solvent
components into a
homogeneous mix of
active ingredients.
Compressed
Gas
A material, or mixture
of materials that
are either liquefied,
nonliquefied, or in
solution having a
boiling point of 68°F
(20°C) or less at
14.7 psia (101.3 kPa)
of pressure. The exceptions
to this rule are those
gases that have no
health or physical
hazard properties.
These gases are not
considered compressed
until the pressure
in their packaging
exceeds 41 psia (282.5
kPa) at 68°F (20°C).
Computer
Controlled System
Computer system plus
its controlled function.
Computer
Related System
Computerized system
plus its operating
environment.
Computer
System
A group of hardware
components and associated
software designed
and assembled to perform
a specific function
or group of functions.
Computerized
System
A process or operation
integrated with a
computer system.
Concavity
(welding)
A condition in which
the surface of a welded
joint is depressed
relative to the surface
of the tube or pipe.
Concavity is measured
as a maximum distance
from the outside or
the inside diameter
surface of a welded
joint along a line
perpendicular to a
line joining the weld
toes.
Concentration
Polarization
The phenomenon in
ultrafiltration (UF)
in which solutes form
a dense, polarized
layer next to the
membrane surface eventually
blocking further flow.
UF systems counteract
this by continuously
flushing the solute
away from the membrane
surface.
Concurrent
Process Validation
Establishing documented
evidence that a process
does what it purports
to do based on information
generated during actual
implementation of
the process.
Condensate
Distillate just after
it has been cooled
from steam into the
liquid state.
Condenser
The heat exchanger
used in distillation
to cool steam in order
to convert it from
the vapor to the liquid
state.
Conductivity
The reciprocal of
resistivity (C=1/R).
A measure of the ability
to conduct an electric
current. Since ionized
impurities increase
the conductivity of
water, it is also
an accurate measure
of ionic purity. Conductivity
is normally expressed
in micromhos/cm (µmho/cm)
or microsiemens/cm
(µS/cm). To measure
it, current is passed
between two electrodes
a fixed distance apart.
Configurable
Software
Commercial, off-the-shelf
software that can
be configured to specific
user applications
without altering the
basic program.
Configuration
The three-dimensional
shape or form of a
macromolecule.
Conformation
The characteristic
three-dimensional
shape (tertiary structure)
of a macromolecule.
Conjugated
Protein
A protein containing
a metal or an organic
prosthetic group or
both. Hemoglobin is
a conjugated protein.
Consent Decree
The result of a serious
violation of federal
regulations and related
safety and quality
standards. A company
must agree to a series
of measures aimed
at bringing its manufacturing
standards in compliance
with federal regulations.
Until agreed-upon
conditions are met,
a company may be forbidden
to distribute its
products in interstate
commerce, except for
those products deemed
essential for the
public health.
Conserved
Sequence
A base sequence in
a DNA molecule (or
an amino acid sequence
in a protein) that
has remained essentially
unchanged throughout
evolution.
Containment
The action of confining
within a defined space
a microbiological
agent or other entity
that is being cultured,
stored, manipulated,
transported, or destroyed
in order to prevent
or limit its contact
with people and/or
the environment. Methods
to achieve containment
include physical and
biological barriers
and inactivation using
physical or chemical
means.
1. Primary Containment.
Addresses the protection
of personnel and the
immediate laboratory
environment from exposure
to infectious agents.
It involves the use
of closed containers
or safety biological
cabinets along with
secure operating procedures.
2. Secondary Containment.
A system of containment
that prevents the
escape of infectious
agents into the environment
external to the laboratory.
It involves the use
of rooms with specially
designed air handling,
the existence of airlocks
and/or sterilizers
for the exit of materials
and secure operating
procedures. In many
cases it may add to
the effectiveness
of primary containment.
1. Appendix G -
Physical Containment
specifies physical
containment for standard
laboratory experiments
and defines Biosafety
Level 1 (BL1) through
Biosafety Level 4
(BL4). (also see:
Biosafety Level, and
Table II - Section
II - Comparison of
Good Large Scale Practice
(GLSP) and Biosafety
Level (BL) - Large
Scale (LS) Practice)
2. Appendix I - Biological
Containment specifies
levels of biological
containment (host
vector systems) for
prokaryotes and defines
Host Vector 1 Systems
(HV1) and Host Vector
2 Systems (HV2). (also
see: Host Vector (HV)
System)
3. Appendix K - Physical
Containment for Large
Scale Uses of Organisms
Containing Recombinant
DNA Molecules specifies
physical containment
guidelines for large
scale (over 10 liters)
research or production
involving viable organisms
containing recombinant
DNA molecules, and
defines GLSP (Good
Large Scale Practice)
through Biosafety
Level 3-LS (Large
Scale). (also see:
Biosafety Level, and
Table II - Section
II - Comparison of
Good Large Scale Practice
(GLSP) and Biosafety
Level (BL) - Large
Scale (LS) Practice)
4. Appendix P - Physical
and Biological Containment
for Recombinant DNA
Research Involving
Plants specifies physical
and biological containment
conditions and practices
suitable to the greenhouse
conduct of experiments
involving recombinant
DNA-containing plants,
plant-associated microorganisms,
and small animals,
and defines Biosafety
Level 1-Plants (BL1-P)
through Biosafety
Level 4-Plants (BL4-P).
5. Appendix Q - Physical
and Biological Containment
for Recombinant DNA
Research Involving
Animals specifies
containment and confinement
practices for research
involving whole animals,
both those in which
the animal's genome
has been altered by
stable introduction
of recombinant DNA,
and experiments involving
viable recombinant
DNA-modified microorganisms
tested on whole animals,
and defines Biosafety
Level 1-Animals (BL1-N)
through Biosafety
Level 4-Animals (BL4-N).
Contaminant
Any unwanted or undesired
component in a process
fluid or controlled
environment.
Contamination
The undesired introduction
of impurities of a
chemical or microbiological
nature, or of foreign
matter, into or onto
a raw material, intermediate,
or API (Active Pharmaceutical
Ingredient) during
production, sampling,
packaging or repackaging,
storage or transport.
Contig
Group of cloned (copied)
pieces of DNA representing
overlapping regions
of a particular chromosome.
Contig Map
A map depicting the
relative order of
a linked library of
small overlapping
clones representing
a complete chromosomal
segment.
Continuous
Fermentation
A process in which
sterile medium is
added without interruption
to the fermentation
system with a balancing
withdrawal (or "harvesting")
of broth for product
extraction. The length
of fermentation can
be measured in weeks
or months. Commercial
applications of continuous
fermentation are limited
in number, with ethanol
production by yeast
the most important
example.
Contract
Manufacturer
A company holding
an agreement requiring
the performance of
some aspect of API
manufacturing
Control Area
A building or portion
of a building within
which the exempted
amounts of hazardous
materials may be stored,
dispensed, handled,
or used.
Control Group
The group of subjects
in a controlled study
that receives no treatment,
receives a standard
treatment, or receives
a placebo.
Control Parameters
Those operating variables
that can be assigned
values and are used
as control levels.
Control Serum
Serum used as a standard
for clinical chemistry
lab tests. Most often
produced from outdated
whole blood plasma.
Most often turbid
and difficult to filter
Controlled
Area
An area constructed
and operated in such
a manner that some
attempt is made to
control the introduction
of potential contamination,
and the consequences
of accidental release
of living organisms.
The level of control
exercised should reflect
the nature of the
organism employed
in the process. At
a minimum, the area
should be maintained
at a pressure negative
to the immediate external
environment and allow
for the efficient
removal of small quantities
of airborne contaminants.
Controlled
Area
Area of restricted
access. A term for
areas and rooms adjoining
a critical area in
aseptic production
facilities.
Conventional
Drugs
New compounds made
up by chemical synthesis
or fermentation. These
are termed by the
FDA as NCEs (New Chemical
Entities). The FDA
rates conventional
drugs with important
therapeutic gain as
1-A drugs, for priority
review. For example,
AIDS drugs are conventional
drugs approved for
AIDS or AIDS-associated
conditions.
Conventional
Flow Cleanroom
A room supplied with
filtered air with
no specified requirement
for uniform airflow
patterns or velocity.
Airflow patterns are
usually turbulent.
Converted
Data
Any original data
that has been entered
into a user-developed
application (spreadsheet,
database, report,
etc.) for manipulation,
evaluation, or review.
Convexity
A condition in which
the surface of a welded
joint is extended
relative to the surface
of the tube or pipe.
Convexity is measured
as a maximum distance
from the outside or
inside diameter surface
of a welded joint
along a line perpendicular
to a line joining
the weld toes.
Corn Steep
Liquor
An ingredient in the
culture medium for
producing penicillin.
A natural nitrogenous
material that is a
by-product of the
corn milling industry.
Corrosive
A chemical that causes
visible destruction
or irreversible alterations
in living tissue by
chemical action at
the site of contact.
A chemical is considered
corrosive if, when
tested on the intact
skin of albino rabbits
by the method described
in Appendix A of CFR
49 Part 173, it destroys
or changes irreversibly
the structure of the
tissue at the site
of contact following
an exposure period
of four hours. This
term shall not refer
to action on inanimate
surfaces.
Corrosive
Liquid
A liquid which when
in contact with living
tissue, will cause
destruction or irreversible
alteration of such
tissue by chemical
action. Examples include
acidic, alkaline,
or caustic materials.
Cosmid
Artificially constructed
cloning vector containing
the cos gene of phage
lambda. Cosmids can
be packaged in lambda
p0hage particles for
infection into E.
coli: this permits
cloning of larger
DNA fragments (up
to 45kb) that can
be introduced into
bacterial hosts in
plasmid vectors.
CP (Cyclic
Polarization)
An electrochemical
test (ASTM G61) for
metals that measures
the point at which
pitting corrosion
begins. CP uses an
electrolytic cell
to directly measure
the corrosion rate.
By using the test
piece as the working
electrode, initiation
of localized corrosion
is shown by the potential
at which the current
density increases
rapidly. This point
is called the "pitting
potential". The
lower the current
density at this point,
the more resistance
to pitting corrosion.
The current density
is measured in micro-amps
per square centimeter.
Critical
A material, process
step, or process condition,
test requirement,
or any other relevant
parameter is considered
critical when non-compliance
with predetermined
criteria directly
influences the quality
attributes of the
API (Active Pharmaceutical
Ingredient) in a detrimental
manner.
Critical
Area
An area where (sterile)
product or contact
surface is exposed,
normally Class 100
(e.g., Point of Fill).
Critical
Device
A device that directly
ensures that a GMP
Critical Parameter
is maintained within
predetermined limits
(e.g., terminal HEPA
filter, point of use
filter). A malfunction
of such a device would
place product quality
directly at risk.
Critical
Instrument
An instrument that
measures a GMP Critical
Parameter, used to
monitor and document
that parameter.
Critical
Parameter
A GMP or product quality
parameter (e.g., differential
pressure, unidirectional
airflow pattern) that
must be maintained
within predefined
limits to ensure product
SISPQ (Strength, Identity,
Safety, Purity, or
Quality).
Critical
Point
The combination of
pressure and temperature
at which the gas and
liquid phases of a
substance become indistinguishable.
Critical
Process Step
For sterile products,
this normally is an
activity where product
or product contact
parts are exposed
to the surrounding
environment.
Critical
Step(s)
The point or points
in the process which,
if not carried out
properly or if contaminated,
will not allow drug
substances to be made
such that they will
meet their intended
characterizations
and impurity profiles.
Critical
Surface
The part of the working
surface to be protected
from particulate contamination.
It is within the Critical
Zone.
Critical
System
A structural, mechanical,
or electrical system
that can impact the
processing parameters
and attributes of
the finished product
or regulatory study.
Critical systems may
include utilities,
process equipment,
and systems.
Cross Contamination
The measurable and
detrimental contamination
of a material or product
with another material
or product.
Crossing
Over
The breaking during
meiosis of one maternal
and one paternal chromosome,
the exchanging of
corresponding sections
of DNA, and the rejoining
of the chromosomes.
This process can result
in an exchange of
alleles between chromosomes.
Cryogenic
Liquid
A fluid that has a
normal boiling point
below -150°F (-101.1°C).
Cryptography
The mathematical science
of deliberately scrambling
and unscrambling information.
Information is protected
by being transformed
(encrypted) into an
unreadable format,
called cipher text.
Only those who posses
a secret key can decypher
(or decrypt) that
message into plain
text.
Culture Medium
Any nutrient system
for the artificial
cultivation of bacteria
or other cells; usually
a complex mixture
of organic and inorganic
materials.
current Good Manufacturing
Practices (cGMP's)
Cut
An enzymatic break
that occurs in both
strands of a DNA molecule
opposite one another
by restriction enzymes.
Cystic Fibrosis
An inherited disease
in which thick mucus
clogs the lungs and
blocks the ducts of
the pancreas.
Cytokine
A protein that acts
as a chemical messenger
to stimulate cell
migration, usually
toward where the protein
is released. Interlukins,
lymphokines, and interferons
are the most common.
Cytolysis
The dissolution of
cells particularly
by destruction of
their cell membrane.
Cytopathic
Damaging to cells.
Cytoplasm
The protoplasmic contents
of the cell outside
the nucleus in which
the cell's organelles
are suspended.
Cytosine
(C)
A pyrimidine occurring
as a fundamental unit
or base of nucleic
acids.
Cytostatic
Agents
Therapeutics that
inhibit cell division
and growth. This term
can refer to machinery,
such as those that
would freeze cells.
Cytotoxic
Poisonous to cells.
Cytotoxicity
The ability of a substance
or compound to cause
a cytotoxic effect.
D
D5W (5 D/W)
One of the most prevalent
of LVPs (also see:
LVP (Large Volume
Parenteral)). Five
percent dextrose in
water. Presence of
dextrose presents
significant filtration
problems. Usually
requires activated
charcoal pretreatment.
Dalton
The unit of molecular
weight, equal to the
weight of a hydrogen
atom.
Data Integrity
The validity of data
and their relationships.
For electronic records
to be trustworthy
and reliable, the
links between raw
data, metadata, and
results must not be
compromised or broken.
Without data integrity,
it is not possible
to regenerate a previous
result reliably.
Data Migration
The process of translating
data from one system
to another when a
company replaces the
current computing
systems with a new
one. CFR 21 Part 11
mandates that data
migration implementation
create accurate and
complete copies of
the records when they
are moved to a new
system.
DDC (Direct
Digital Control)
A collection of control
units (analog and
discrete) connected
into a data highway,
usually with a host
or alarming/recording
computer attached.
D Value
The time under a stated
set of exposure conditions
(temperature in an
autoclave) required
to reduce a microbial
population by a factor
of 90% (e.g. from
10,000 to 1,000).
Dead Leg
An area of entrapment
in a vessel or piping
run that could lead
to contamination of
the product. In a
piping system, a non-flowing
pocket, tee, or extension
from a primary piping
run that exceeds a
defined number of
pipe diameters from
the ID of the primary
pipe. Denoted by the
term L/D or L/A, where
L is equal to the
leg extension perpendicular
to the normal flow
pattern or direction,
A is the annular gap
width, and D is equal
to the ID (or inside
dimension) of the
extension or leg.
In some existing standards,
the dimension L is
measured from the
centerline of the
primary pipe. For
bioprocessing systems,
an L/D of 2:1 is achievable
with today's component
technology for most
valving and piping
configurations.
Decontamination
A process that reduces
contaminating substances
to a defined acceptance
level.
Deflagration
An exothermic reaction,
such as the extremely
rapid oxidation of
a combustible dust
or flammable vapor
in air, in which the
reaction progresses
through the unburned
material at a rate
less than the velocity
of sound. A deflagration
can have an explosive
effect.
Degrading
Deterioration of a
surface finish so
that pieces of the
finish (or substrate)
material large enough
to be visible to the
unaided eye, dislodge
without any direct
physical contact and
fall from the surface
of the material.
Deionization
Removing dissolved
ions from solution
by passing the solution
through a bed of ion
exchange resin, consisting
of polymer beads that
exchange hydrogen
ions for cations and
hydroxyl ions for
anions in solution.
The ionic impurities
remain bound to the
resins and the hydrogen
and hydroxyl ions
combine with each
other to form water.
Deletion
Map
A description of a
specific chromosome
that uses defined
mutations - specific
deleted areas in the
genome - as "biochemical
signposts", or
markers for specific
areas.
De Minimis
Release
The release of viable
microbiological agents
or eukaryotic cells
that does not result
in the establishment
of disease in healthy
people, plants, or
animals; or in uncontrolled
proliferation of any
microbiological agents
or eukaryotic cells.
Dementia
Severe impairment
of mental functioning.
Demineralization
Sometimes used interchangeably
with deionization,
it refers to the removal
of minerals and mineral
salts using ion exchange.
