N
National electrical
Code®
The electrical code
used throughout the
United States. Published
by the National Fire
Protection Association
(NFPA), it is an indispensable
aid to every electrician,
contractor, architect,
builder, inspector,
and anyone who must
specify or certify electrical
installations.
National Formulary
(NF)
A compendium of purity
and testing criteria
for chemicals, usually
used in combination
with the USP.
Necrosis
The pathological death
of one or more cells,
or of a portion of tissue
or organ, resulting
from irreversible damage
to the nucleus.
NEMA (National Electrical
Manufacturers Association)
Enclosures As a way
of standardizing enclosure
performance, NEMA uses
a rating system to identify
the enclosure's ability
to resist external environmental
influences. Resistance
to everything from dripping
liquid to hose-down
to total submersion
is defined by this rating
system.
1. Type 1 - Enclosures
constructed for indoor
use to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment
and to provide a degree
of protection against
falling dirt.
2. Type 2 - Enclosures
constructed for indoor
use to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment,
to provide a degree
of protection against
falling dirt, and to
provide a degree of
protection against dripping
and light splashing
of liquids.
3. Type 3 - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt, rain,
sleet, snow, and windblown
dust; and that will
be undamaged by the
external formation of
ice on the enclosure.
4. Type 3R - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt, rain,
sleet, and snow; and
that will be undamaged
by the external formation
of ice on the enclosure.
5. Type 3S - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt, rain,
sleet, snow, and windblown
dust; and in which the
external mechanism(s)
remain operable when
ice laden.
6. Type 4 - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt, rain,
sleet, snow, and windblown
dust, splashing water,
and hose-directed water;
and that will be undamaged
by the external formation
of ice on the enclosure.
7. Type 4X - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt, rain,
sleet, snow, and windblown
dust, splashing water,
hose-directed water,
and corrosion; and that
will be undamaged by
the external formation
of ice on the enclosure.
8. Type 5 - Enclosures
constructed for indoor
use to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
settling airborne dust,
lint, fibers, and flyings;
and to provide a degree
of protection against
dripping and light splashing
of liquids.
9. Type 6 - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
hose-directed water
and the entry of water
during occasional temporary
submersion at a limited
depth; and that will
be undamaged by the
external formation of
ice on the enclosure.
10. Type 6P - Enclosures
constructed for either
indoor or outdoor use
to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
hose-directed water
and the entry of water
during prolonged submersion
at a limited depth;
and that will be undamaged
by the external formation
of ice on the enclosure
11. Type 12 - Enclosures
constructed (without
knockouts) for indoor
use to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
circulating dust, lint,
fibers, and flyings;
and against dripping
and light splashing
of liquids.
12. Type 12K - Enclosures
constructed (with knockouts)
for indoor use to provide
a degree of protection
to personnel against
incidental contact with
the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
circulating dust, lint,
fibers, and flyings;
and against dripping
and light splashing
of liquids.
13. Type 13 - Enclosures
constructed for indoor
use to provide a degree
of protection to personnel
against incidental contact
with the enclosed equipment;
to provide a degree
of protection against
falling dirt; against
circulating dust, lint,
fibers, and flyings;
and against the spraying,
splashing, and seepage
of water, oil, and noncorrosive
coolants.
Neoplasm
Any new growth of cells
or tissues but the term
is customarily used
with rather specific
reference to a focus
(or a relatively large
mass or region) of intermittently
or constantly progressive,
comparatively unlimited,
or uncontrolled new
growth that manifests
varying degrees of autonomy.
Nephelometer
Any apparatus used to
measure the size and
concentration of particles
in a liquid by analysis
of light transmitted
through or reflected
by the liquid.
Nephelometry
The semiquantitative
estimation of the concentration
of particles in a suspension
(e.g. bacterial cells
in an antigenic preparation),
by means of comparing
it with the standard
suspensions in a nephelometer.
Nephrotoxin
A cytotoxin that is
specific for cells of
the kidney.
New Drug Application
(NDA)
The New Drug Application
contains most of the
information included
in the IND. Only after
FDA approval of the
NDA, can distribution
and marketing of a new
drug begin.
NHSA (Normal Human
Serum Albumin)
A blood plasma fraction
usually prepared by
Cohn cold ethanol precipitation.
Dispensed as a 5% to
25% protein solution.
NIH (National Institutes
of Health)
Guidelines NIH Guidelines
specify practices for
constructing and handling
recombinant deoxyribonucleic
acid (DNA) molecules,
and organisms and viruses
containing recombinant
DNA molecules.
Nitrogenous Base
A nitrogencontaining
molecule that has the
chemical properties
of a base.
Nominal A numerical
identification of dimension,
capacity, rating, or
other characteristics
used as a designation,
not as an exact measurement.
Nominal (Rating of Filter)
An arbitrary micrometer
value indicated by filter
manufacturers. Based
upon removal of some
percentage of particles
of a given size or larger,
but rarely well defined
and consequently not
reproducible.
Nominal Pore Size
Based on retention efficiency,
a filter should retain
99.9% of particles larger
than its nominal rated
pore size.
Nominal Outside Diameter
A numerical identification
of outside diameter
to which tolerances
apply.
Nominal Wall Thickness
A numerical identification
of wall thickness to
which tolerances apply.
Noncarbonate Hardness
Hardness in water caused
by chlorides, sulfates,
and nitrates of calcium
and magnesium.
Non-GMP Technology
Facility design requirement
resulting from decisions
to address issues outside
the realm of GMPs or
manufacturer preferences.
Often these do affect
GMP related design features.
Non-Laminar Airflow
Nonunidirectional Airflow
Air distribution where
the first air entering
the controlled space
mixes with the internal
air by means of induction.
The airflow that does
not meet the definition
of unidirectional airflow;
previously referred
to as "turbulent"
or "non-laminar"
airflow.
Normal Saline
A very common LVP that
has a physiologic (0.9gm%)
concentration of sodium
chloride.
Northern Blot
A recombinant DNA technique
used for the detection
of specific RNA transcripts.
Not Exposed or Closed
Drug substance is protected
from exposure to the
environment during processing.
NPDWR Water
Potable water meeting
EPA National Primary
Drinking Water Regulations.
Nuclease
An enzyme that breaks
down nucleic acids.
Exonucleases cleave
the nucleotides only
at the ends of polynucleotide
chains (e.g. phosphodiesterase).
Endonucleases attack
certain linkates wherever
they occur in the polynucleotide
chain
Nucleic Acid
A large molecule composed
of nucleotide subunits.
Nucleic Acid Hybridization
Matching of either DNA
or RNA (depending on
the organism) from an
unknown organism with
DNA or RNA from a known
organism. This method
is used in tropical
disease research for
identifying species
and strains of organisms.
Nucleoid
The compact body that
contains the genome
in a bacterium.
Nucleolus
A discrete region of
the nucleus created
by the transcription
of rRNA genes. The nucleolus
disappears during mitosis,
or cell division.
Nucleotide
The structural unit
of nucleic acids. A
subunit of DNA or RNA
consisting of purine
bases (adenine, guanine),
pyrimidine bases (thymine,
or cytosine in DNA;
uracil, or cytosine
in RNA), a phosphate
molecule, and a sugar
molecule (deoxyribose
in DNA and ribose in
RNA). Thousands of nucleotides
are linked to form a
DNA or RNA molecule.
Nucleus
The cellular organelle
present in eukaryotes
cells and separated
from the cytoplasm by
a nuclear membrane.
It contains the genetic
material and is essential
for the continued life
of the cell.
O
Object Database Management
System (ODBMS)
A database management
system specifically
designed to manage and
store complex objects
and their complex relationships;
that is, such items
are stored as objects
rather than as tables
or fields. They support
modeling and creation
of data as objects,
allowing for greater
flexibility in tracking
parent method sets and
subcomponents. Such
systems may be better
than relational database
management systems at
meeting the data integrity
requirements of CFR
21 Part 11.
Occupancy
The purpose for which
a building or part thereof
is used or intended
to be used.
Occupancy Classification
ODBMS
Ohm
Unit of electrical resistance
in a circuit, such that
a potential difference
of one volt across a
load of one ohm produces
a current of one ampere.
Oncogene
A gene that when expressed
as a protein can lead
cells to become cancerous,
usually by removing
the normal constraints
on growth.
Open
Exposed to the environment,
not closed.
Open System
A system that fails
to meet one or more
of the requirements
that set the criteria
for a closed system.
Operating Parameter
Any information entered
into an automated system
that is used for automated
equipment operation.
Or, a parameter indicative
of the operating condition
of a system.
Operating Range
The validated acceptance
criteria within which
a control parameter
must remain, wherein
acceptable product is
being manufactured.
Operating System (OS)
The most important program
run on a computer because
it manages all the other
programs. Operating
systems perform basic
tasks, such as recognizing
input from the keyboard,
sending output to the
display screen, keeping
track of files and directories
on the disk, and controlling
peripheral devices such
as disk drives and printers.
For large systems, the
OS has even greater
responsibilities and
powers. It regulates
traffic, making sure
that different programs
and users running at
the same time do not
interfere with each
other. The operating
system also is responsible
for security, ensuring
that unauthorized users
do not access a system.
Microsoft Windows NT,
LINUX, and UNIX are
operating systems.
Operating Variables
All factors of operation,
including control parameters
that may potentially
affect process state
of control and/or fitness
for use of the product.
Operation
Room condition when
normal process operations
are undertaken.
"Operational"
Cleanroom
ISO 14644-1 defines
"operational"
occupancy state as "condition
where the installation
is functioning in the
specified manner, with
the specified number
of personnel present
and working in the manner
agreed upon". (
Ophthalmic
Of, or relating to the
eye, ocular.
Ophthalmics
Pertaining to products
for the eyes. GMP requirements
for the preparation
of ophthalmics are essentially
identical to those for
parenterals.
OQ (Operational Qualification)
Documented verification
that aspects of a facility
system that can affect
product quality perform
as intended throughout
anticipated operating
ranges.
Oral
Relating to the mouth.
Oral Product
A pharmaceutical product
meant to be introduced
through the mouth in
the form of a tablet,
capsule, or suspension.
Oral Solid Dosage Drug
Formulated in a solid
or powder form for patient
to ingest orally.
Orbital Welding
Automatic or machine
welding of tubes or
pipe in-place with the
electrode rotating (or
orbiting) around the
work. Orbital welding
can be done with the
addition of filler material
or as a fusion process
without the addition
of filler.
Organelles
Membrane-surrounded
structures found in
eukaryotic cells; they
contain enzymes and
other components required
for specialized cell
function.
Organic
Organic matter is a
broad category that
includes both natural
and man-made molecules
containing carbon and
hydrogen. All living
matter in water is made
up of organic molecules.
The most common are
by-products of vegetative
decay such as tannins,
lignins, and humic acid.
Organic Peroxide
An organic compound
that contains the bivalent
-0-0- structure and
which may be considered
to be a structural derivative
of hydrogen peroxide
where on or both of
the hydrogen atoms have
been replaced by an
organic radical. Organic
peroxides can present
an explosion hazard
(detonation or deflagration)
or they can be shock
sensitive. They can
also decompose into
various unstable compounds
over an extended period.
Organism
A single, autonomous
living thing. Bacteria
and yeasts are organisms;
mammalian and insect
cells used in culture
are not.
Origin
Point or region where
DNA replication is begun.
Often abbreviated Ori.
Orphan Drug
The FDA grants Orphan
Drug status to one company
for a drug that is believed
to substantially increase
the life expectancy
of the treated patient
for a particular disease.
This excludes other
companies from receiving
an FDA license to produce
a similar drug for a
finite period (usually
7 years), thereby allowing
the company producing
the drug to recuperate
their R&D expenses.
OS
Osmosis
The diffusion of a solvent
through a semipermeable
membrane from a solution
of higher concentration
to one of lower concentration
until there are equal
concentrations of fluid
on both sides of the
membrane.
Osmotic Pressure
Pressure generated by
the osmotic flow of
water through a membrane
into a (aqueous) phase
containing a solute
in a higher concentration.
Out of Specification
An examination, measurement,
or test result that
does not comply with
preestablished criteria.
Overlapping Clones
Oxidation (on metals)
The formation of an
oxide layer on a metal
surface. When oxidation
occurs because of welding,
it is visible as discoloration.
The discoloration or
heat tint produced by
oxidation has been associated
with the onset of corrosion
in stainless steel piping
systems.
Oxide Thickness
The depth at which the
oxide signal has fallen
to half the maximum
peak height. Typical
values for well electropolished
316L stainless steel
range from 20 to 50
angstroms (Å).
Oxide Layer
In welding, an area
usually located in the
heat-affected zone (HAZ)
of the weldment where
an oxidation reaction
has taken place.
Oxidizer
A material other than
a blasting agent or
explosive, that readily
yields oxygen or other
oxidizing gas, or that
readily reacts to promote
or initiate combustion
of combustible materials.
Oxidizers are subdivided
as follows:
1. Class 4 - An oxidizer
that can undergo an
explosive reaction due
to contamination or
exposure to thermal
or physical shock. In
addition, the oxidizer
will enhance the burning
rate and may cause spontaneous
ignition of combustible
materials.
2. Class 3 - An oxidizer
that will cause a severe
increase in the burning
rate of combustible
materials with which
it comes in contact
or that will undergo
vigorous, self-sustained
decomposition due to
contamination or exposure
to heat.
3. Class 2 - An oxidizer
that will cause a moderate
increase in the burning
rate or that may cause
spontaneous ignition
of combustible materials
with which it comes
in contact.
4. Class 1 - An oxidizer
whose primary hazard
is that it slightly
increases the burning
rate but does not cause
spontaneous ignition
when it comes in contact
with combustible materials.
Ozone
Formed by an electric
discharge or by the
slow combustion of phosphorus,
ozone is a modified
and condensed form of
oxygen, in which three
atoms of oxygen are
combined to form the
molecule, O3. Because
it is a powerful oxidizing
agent it is used in
deionized water systems
to kill bacteria and
to reduce by oxidation
the amount of Total
Organic Carbon (TOC)
in the water. Air containing
a perceptible amount
of ozone has an odor
suggesting chlorine
or sulfurous acid gas.
P
Packaged Equipment
An assembly of individual
pieces or stages of
equipment, complete
with inter-connecting
piping and connections
for external piping.
The assembly may be
mounted on a skid or
other structure prior
to delivery.
Packaging
All operations, including
filling and labeling,
which a bulk product
has to undergo in order
to become a finished
product.
Packaging Material
Any material intended
to protect an intermediate
or API (Active Pharmaceutical
Ingredient) during storage
and transport.
Pandemic Disease
An epidemic over an
especially wide geographic
area.
PAR (Proven Acceptable
Range)
A range for a critical
parameter that has been
determined to be achievable
and appropriate for
the process or processes
with which it is associated.
It is established by
knowledge gained through
relevant documentation
and actual testing.
A process should perform
consistently and as
intended when all critical
parameters are held
within the established
PARs.
Parenteral Drug (LVP,
SVP)
A parenteral drug is
defined as one intended
for injection through
the skin or other external
boundary tissue, rather
than through the alimentary
canal, so that active
substances they contain
are administered, using
gravity or force, directly
into a blood vessel,
organ, tissue, or lesion.
They are infused when
administered intravenously
(IV), or injected when
administered intramuscularly
(IM), or subcutaneously
into the human body.
A large volume parenteral
(LVP) is a unit dose
container of greater
than 100ml that is terminally
sterilized by heat.
Small volume parenteral
(SVP) is a "catch-all"
for all non-LVP parenterals
products except biologicals.
Particle
Solid or liquid object
which for purposes of
classification of air
cleanliness, falls within
a cumulative distribution
that is based upon a
threshold (lower limit)
size in the range from
0,1 µm to 5 µm. ISO
14644-1
Particle Size
The apparent maximum
linear dimension of
a particle in the plane
of observation as seen
with a microscope or
the equivalent diameter
of a particle detected
by automatic instrumentation.
The equivalent diameter
is the diameter of a
reference sphere having
known properties and
producing the same response
in the sensing instrument
as the particle being
measured. ISO 14644-1
Particle Concentration
Number of individual
particles per unit volume
of air. ISO 14644-1
Particulate Usually
a solid particle large
enough to be removed
by filtration. Nonfilterable
solids are usually referred
to as colloids.
Parts Per Billion (PPB)
(also see: PPB)
Parts Per Million (PPM)
(also see: PPM)
Passive Immunity
Temporary immunity produced
by administration of
gamma globulin.
Passivity
The state in which a
stainless steel exhibits
a very low corrosion
rate. Also known as
passivity, is the loss
(or minimizing) of chemical
reactivity exhibited
by certain metals and
alloys under special
environmental conditions.
Passivation
A final chemical treatment/cleaning
process that removes
exogenous iron or iron
compounds from the surface
of stainless steel piping
and equipment by the
use of a mild oxidant,
such as a nitric acid
solution, or by "in-situ
electropolishing. The
purpose of passivation
is to restore and/or
enhance the spontaneous
formation of the chemically
inert surface or protective
passive film.
Passive Layer
A passive oxidized film
that forms naturally
on a stainless steel
surface when exposed
to air or similar oxidizing
environment thus protecting
the underlying base
metal from corrosion.
Welding disturbs the
passive layer by reducing
the chromium and increasing
the iron, thus altering
the chromium/iron ratio
(measure of corrosion
resistance). Upon completion
and approval of the
weld, the weld surface
and adjacent boundary
area must be brought
back to a passive state.
Additionally, normal
operating conditions
in typical Water For
Injection, reverse osmosis,
deionized water, clean
steam, Clean In Place,
and process piping often
lead to formation of
the most prevalent form
of self catalyzing corrosion
called "rouge"
(French for red), which
is a colloidal form
of rust containing iron
oxide, chromium and
nickel in various forms.
This problem is further
accentuated by high
temperature. The rouge
layer acts as a passive
layer until it becomes
so thick that it "sloughs
off" into the process
or water stream.
Pasteurization
The heating of milk,
wines, fruit juices,
etc., for about thirty
minutes at 68°C (154.4°F)
whereby the living bacteria
are destroyed, but the
flavor or bouquet is
preserved; the spores
are unaffected, but
are kept from developing
by immediately cooling
the liquid to 10°C (50°F)
or lower.
Pathogen
Any microbiological
or eukaryotic cell containing
sufficient genetic information,
which upon expression
of such information
is capable of producing
disease in healthy people,
plants, or animals.
Pathogenic
Causing or capable of
causing disease.
Pathogenic Organisms
Organisms capable of
causing disease, either
directly (by infecting)
or indirectly (by producing
a toxin that causes
illness).
PE (Polyethylene)
A thermoplastic material
that varies from type
to type according to
the particular molecular
structure of each type,
i.e. its crystallinity,
molecular weight, and
molecular weight distribution.
These variations are
possible through changes
in polymerization conditions
used during manufacturing.
Low-density polyethylene
(LDPE) has a melt point
of 221°F (105°C), specific
gravity of 0.91 to 0.925
g/cc, increased toughness,
stress cracking resistance,
clarity, flexibility,
and elongation. It also
has reduced creep and
mold shrinkage. Polyethylene
of higher density such
as HDPE has better permeation
barrier properties,
hardness, abrasion resistance,
chemical resistance,
and surface gloss. It
is important to note
that photo or light
oxidation will occur
when natural PE is exposed
to UV radiation, usually
from the sun.
Penetrance
A term indicating the
likelihood that a given
gene will actually result
in disease.
Penicillin
An antibiotic containing
a ß-lactam ring that
inhibits an enzyme responsible
for making peptide cross-links
in the bacterial cell
wall. It is obtained
from cultures of the
molds Penicillium Notatum
or Penicillium Chrysogenum.
Penicillium
The genus of mold causing
a zone of inhibition
in an agar plate of
bacteria. It is the
organism, which produces
natural penicillin.
Peptide A secondary
protein derivative defined
as "a definitely
characterized combination
of two or more amino
acids, the carboxyl
(COOH) group of one
being united with the
amino (NH2) group of
the other, with the
elimination of a molecule
of water". They
form a peptide bond.
Peptide Hormones
A diverse class of hormones
that are synthesized
and excreted at various
sites within the body.
Examples include: insulin,
relaxin, glucagons,
growth hormone, vasopressin,
ACTH (Adrenocorticotropic
Hormone), endorphins,
and encephalins.
Percent Recovery
In reverse osmosis or
ultrafiltration, the
ratio of pure water
output to feedwater
input.
Percent Rejection
In reverse osmosis or
ultrafiltration, the
ratio of impurities
removed to total impurities
in the incoming feedwater.
For example, RO membranes
typically remove (reject)
90% of the dissolved
inorganic contaminants
in water.
Peristaltic Pump
A type of positive displacement
pump that operates by
pulsations of flow caused
by passing rollers over
flexible tubing. Operating
pressure limited by
tubing tolerance.
Permeability
he ability of a body
to pass a fluid under
pressure.
Permeate In reverse
osmosis, the water that
diffuses through the
membrane, thereby becoming
purified water.
Permissible Exposure
Limit (PEL)
The maximum permitted
eight-hour time-weighted
average concentration
of an airborne contaminant.
For Permissible Exposure
Limits see CFR 29 -
1910.1000.
Permissions or Privileges
Security codes that
define or restrict which
users can read, write,
and execute the associated
files, directories,
or programs. Some departments
need to look only at
data, some need to input
data or run programs,
and others may not need
to look at the data
at all.
Peroxisome
Very small membrane-bound
particles responsible
for photorespiration
in plants. Similar to
lysosome in structure,
but not in function.
Petrolatum
White petrolatum is
a purified mixture of
semi-solid hydrocarbons
obtained from petroleum.
It is a common base
or carrier for ointments.
It can be sterile filtered
at elevated temperatures.
pH
The pH value of an aqueous
solution is a number
describing its acidity
or alkalinity. A pH
is the negative logarithm
(base 10) of the concentration
of hydrogen ions (equivalent
per liter). The pH value
of a neutral solution
is 7. An acidic solution
has a pH less than 7,
while a basic solution
has a pH greater than
7, up to 14.
Phage
A virus for which the
natural host is a bacterial
cell. (also see: Bacteriophage)
Phagocyte A cell that
engulfs foreign particles
from its surroundings
by a process called
phagocytosis. The cell
releases hydrolytic
enzymes from intracellular
bodies called lysosomes
that partially digest
the foreign particle,
after which it is further
degraded in the phagocyte
cytoplasm.
Pharmaceutical
A medicinal drug, or
relating to or engaged
in pharmacy or the manufacture
and sale of pharmaceuticals.
A pharmaceutical product
is generally one that
is made up using available
chemical compounds.
Pharmaceutical Area
A general manufacturing
area classification
designated by the need
for a change of clothing
(e.g., Packing Hall).
See ISPE® Sterile Baseline
Guide.
Phenol
An organic acid often
used as a disinfectant.
Proper strength for
a bacteriocidal preparation
is 5%. Sometimes dispersed
as an aerosol "fog"
in manufacturing rooms.
Physical Hazard
A classification of
a chemical for which
there is scientifically
valid evidence that
it is a combustible
liquid, compressed gas,
cryogenic, explosive,
flammable gas, flammable
liquid, flammable solid,
organic peroxide, oxidizer,
pyrophoric, unstable,
(reactive), or water-reactive
material.
Photoautotrophs
Facultative autotrophs
that obtain their energy
from light.
Photoluminescent
The property of emitting
light as the result
of absorption of visible
or invisible light,
which continues for
a length of time after
excitation.
Photo Oxidation
The mechanism by which
ultraviolet light reduces
Total Organic Carbon
(TOC) to Carbon Dioxide.
If halogenated organics
are present, both CO2
and mineral acids can
be formed.
Phycomycetes Algalike
fungi that do not posses
chlorophyll and cannot
photosynthesize. Aquatic
and terrestrial molds
belong to this category.
Physical Barrier
Any equipment, facilities,
or devices (e.g., fermentors,
factories, filters,
thermal oxidizers) that
are designed to achieve
containment.
Physical Manipulation
A process other than
a chemical reaction
that may change the
purity of the physical
properties of the material,
including but not limited
to, crystallization,
recrystallization, gel
filtration, chromatography,
milling, drying, or
blending.
Physical Map
A map of the locations
of identifiable landmarks
on DNA (e.g., restriction
enzyme cutting sites,
genes), regardless of
inheritance. Distance
is measured in base
pairs. For the human
genome, the lowest-resolution
physical map is the
banding patterns on
the 24 different chromosomes;
the highest resolution
map would be the complete
nucleotide sequence
of the chromosomes.
Pickle
An acid or other chemical
solution used as a bath
to remove scale and
oxides fro the surface
of metals before plating
or finishing.
Pipe
A pressure-tight cylinder
used to convey a fluid
or to transmit a fluid
pressure ordinarily
designated "pipe"
in applicable material
specifications. Materials
designated "tube"
or "tubing"
in the specifications
are treated as pipe
when intended for pressure
service. Types of pipe,
according to the method
of manufacture, are:
1. Electric resistance-welded
pipe (ERW) 2. Furnace
butt welded pipe, continuous
welded 3. Electric-fusion
welded pipe 4. Double
submerged-arc welded
pipe 5. Seamless pipe
6. Spiral welded pipe
Pipe Size
Pipe size is determined
by diameter and schedule.
For bioprocessing equipment,
pipe does not include
tube.
Pit
A small surface void
resulting from a localized
loss of base metal by
corrosion or etching,
or by the removal of
surface inclusions during
electropolishing or
passivation. A pit may
or may not be detectable
during liquid penetrant
inspection.
Pitch
To cause to be set at
a particular angle or
slope. Degree of slope
or elevation.
Placebo
An inert or innocuous
substance used in controlled
experiments testing
the efficacy of another
substance.
Plankton
Those microorganisms
that are passively floating
or drifting in a body
of water.
Plaque A clear zone
in a bacterial culture
grown on an agar plate
caused by localized
destruction of bacterial
cells by a bacteriophage.
Applying the fluid to
a culture and counting
the number of plaques
formed can estimate
the concentration of
infective virus in a
fluid.
Plasma
The liquid portion of
blood in which the cellular
elements are suspended.
As a fresh liquid obtained
by centrifugation, plasma
is a clear, amber-colored
solution containing
eight to nine percent
solids; of these, 85
percent are proteins
while the other components
are the lipids, which
include the neutral
fats, fatty acids, lecithin,
and cholesterol. Also
present are sodium,
chloride and bicarbonate,
potassium, calcium and
magnesium. A most essential
function of plasma is
the maintenance of blood
pressure and the exchange
with tissue of nutrients
for waste. Contains
fibrinogen.
Plasma Cell
A cell derived from
a B-lymphocyte and solely
responsible for the
production of antibodies.
Each plasma cell forms
only one type of antibody
and is characterized
by an eccentric nucleus,
a prominent Golgi zone,
bulky basophilic cytoplasm
(due to an extensive
endoplasmic reticulum)
and large numbers of
mitochondria.
Plasma Membrane
The physical barrier
that surrounds the cytoplasm
of all cells. It is
composed of lipid, protein,
and carbohydrate and
is semi-permeable.
Plasma Proteins
The proteins found in
plasma, usually divided
into albumin, globulin
and fibrinogen fractions.
Plasma Protein Fraction
(PPF)
Plasmid
Self-replicating, extrachromosomal
circular DNA molecules,
distinct from the normal
bacterial genome and
nonessential for the
cell survival under
nonselective conditions.
Some plasmids are capable
of integrating into
the host genome. A number
of artificially constructed
plasmids are used as
cloning vectors.
Plastics
High molecular weight
polymers or copolymers.
The wide range in physical
properties of polymeric
materials allows for
utilization as elastomers,
fibers, adhesives, rigid
castings, composites,
and laminates. ASTM
D883 defines a plastic
as a material that contains
as an essential ingredient,
one or more organic
polymeric substances
of large molecular weight,
is solid in its finished
state, and, at some
stage in its manufacture
into finished articles,
can be shaped by flow.
Plastics, or more appropriately
polymers, are composed
primarily of carbon,
hydrogen, oxygen, silicon,
chlorine, fluorine,
and nitrogen, in various
combinations and permutations.
Plastics are grouped
into two categories:
1. Thermoplastics: can
be melted, cooled and
remelted without destroying
the physical or mechanical
characteristics of the
polymer. This property
permits components to
be molded or extruded.
Thermoplastic polymers
include: Chlorinated
Vinyls, Fluorinated
plastics, Ketone, Nitrile,
Nylon, Polyamide-imide,
Polyolefin, Polycarbonate,
and Acrylonitrile butadiene
styrene (ABS). (also
see: Chlorinated Vinyls,
Fluorinated Plastics,
Polyolefin) 2. Thermosets:
begin as a liquid or
powder that through
chemical reaction with
a second reactant or
through catalyzed polymerization
result in anew product
with characteristics
different from either
starting material. Thermoset
resins include: Epoxy,
Phenolic, Polyurethane,
Silicone, Urea and Melamine,
Polyester, Vinyl ester,
Furan, Bisphenol A fumarate.
Plastics, U.S.P. Classification
(also see: Biological
Reactivity Tests, In
Vivo)
Pleuropneumonia
A specific infectious
disease in cattle characterized
by inflammation of the
lung and pleura, generally
called contagious pleuropneumonia.
It is due to a virus.
Plena
The plural of plenum.
Plenum
An enclosure in which
air or other gas is
at a pressure greater
than that outside the
enclosure.
PLC (Programmable Logic
Controller)
An automated system
with analog capability
as well as binary (discrete).
PLCs must be equipped
with a digital interface
to a "front end"
computer for data collection
and for programmer interface.
PLC Controlled Automated
System
Any automated system
using a Programmable
Logic Controller as
its primary controller.
Plumbing Code
Poison
Any substance which
when taken into the
body in a single dose
of 1.0 gm. or less,
is injurious to health
or dangerous to life.
Polyalphaolefin (PAO)
A synthetic oil used
in lieu of DOP for HEPA
filter testing.
Polygenic Disorder
Genetic disorder resulting
from the combined action
of alleles of more than
one gene (e.g., heart
disease, diabetes, and
some cancers). Although
such disorders are inherited,
they depend on the simultaneous
presence of several
alleles; thus the hereditary
patterns are usually
more complex than those
of single gene disorders.
Polyolefin
The polyolefin polymer
is probably one of the
most economical and
widely used classes
of thermoplastics, including
such materials as PB,
PP, and PE. PB is a
semicrystalline polymer
based on polybutene,
homopolymers, and either
polybutene or polyethylene
copolymers. The primary
use of PB is pipe with
hydrostatic pressure
rating of 1,000 psi
at 73°F. PP is a crystalline
polymer that has good
resistance to caustics,
solvents, acids, and
other organic chemicals,
but is not resistant
to oxidizing-type acids,
detergents, alcohols,
or chlorinated organic
materials. It is suitable
for pipe applications.
The largest group of
polyolefins is linear
PE. It includes ULDPE,
LLDPE, LDPE, HDPE, HMW-HDPE,
and UHMWPE. These density
descriptions generally
refer to ASTM designations
based on unmodified
polymers. PE types of
higher density have
better permeation barrier
properties, hardness,
abrasion resistance,
chemical resistance,
and higher surface gloss.
Polished Water
High purity water after
it has undergone a second
treatment step. Ultrapure
water usually undergoes
two or more treatment
steps. More economical
pretreatment processes
(e. g., reverse osmosis)
are used to remove all
but a very small fraction
of the impurities. Highly
efficient polishing
processes (e. g., mixed-bed
deionization) are used
to remove the impurities
that remain.
Polymer
A macromolecule (long
chain) consisting of
five or more repeating
units called monomers.
Examples include polyethylene,
polystyrene, and PTFE
(polytetrafluoroethylene).
Polymerase
An enzyme that catalyzes
production of nucleic
acid molecules.
Polymerase Chain Reaction
(PCR)
A method for amplifying
a DNA base sequence
using a heatstable polymerase
and two 20-base primers,
one complementary to
the (+) strand at one
end of the sequence
to be amplified and
the other complementary
to the (-) strand at
the other end. Because
the newly synthesized
DNA strands can subsequently
serve as additional
templates for the same
primer sequences, successive
rounds of primer annealing,
strand elongation, and
dissociation produce
rapid and highly specific
amplification of the
desired sequence. PCR
also can be used to
detect the existence
of the defined sequence
in a DNA sample.
Polymorphism
Difference in DNA sequence
among individuals. Genetic
variations occurring
in more than 1% of a
population would be
considered useful polymorphisms
for genetic linkage
analysis. (also see:
Mutation
Polypeptide
A long chain of amino
acids covalently bound
by peptide.
Porcine
Of, relating to, or
from swine (pigs) such
as porcine growth hormone.
Positional Cloning
A technique used to
identify genes, usually
those that are associated
with diseases, based
on their location on
a chromosome. This is
contrast to the older,
"functional cloning"
technique that relies
on some knowledge of
a gene protein product.
For most diseases, researchers
have no such knowledge.
Positive Pressure Personnel
Suit
Personnel protection
equivalent to that provided
by Class III (BSCs).
It is a one-piece, ventilated
suit worn by the laboratory
worker when working
with Biosafety Level
3 (BL-3) or Biosafety
Level 4 (BL-4) in a
"suit area"
and using Class I or
II Biological Safety
Cabinets (BSCs). The
personnel suit is maintained
under positive pressure
with a life-support
system to prevent leakage
into the suit. In this
containment system,
the worker is isolated
from the work materials.
The personnel suit area
must be entered through
an airlock fitted with
airtight doors. A chemical
shower is provided as
a "dunk tank"
to decontaminate the
surfaces of the suit
as the worker leaves
the area. The exhaust
air from the suit area
is filtered through
two HEPA filters installed
in series. The entire
area must be under negative
pressure.
Potable
Suitable for drinking.
Potent
A substance that is
"active" in
relatively low doses
or concentrations.
PP (Polypropylene)
A crystalline polymer
with a melting point
of 330°F (165°C), and
heat deflection temperature
ranging from 195°F (91°C)
to 240°F (116°C) which
is higher than other
common plastics. Its
key properties are high
heat resistance (for
piping an upper limit
of 212°F (100°C)), a
specific gravity of
0.91 if unmodified (the
lightest of the most
common thermoplastics),
stiffness, and chemical
resistance with respect
to handling caustics,
solvents, acids, and
other organic chemicals.
It is not recommended
for use with oxidizing
type acids, detergents,
low boiling hydrocarbons,
alcohols, and some chlorinated
organic materials. Polypropylene
is a relatively inert
material and contributes
little in the way of
contamination to pharmaceutical
water.
PPB (Parts Per Billion)
Parts per billion (abbreviated
ppb only in the U.S.),
or micrograms per liter.
One part per billion
is like seeing a bottle
cap on the earth's equator
from an orbiting satellite.
PPF
A blood plasma fraction.
Identical to NHSA (also
see: NHSA, ISG) but
containing no more than
15% w/w A and ß globulins.
Dispensed as a 5% solution.
PPLO
Pleuropneumonia Like
Organism.
PPM (Parts Per Million)
Abbreviation for parts
per million, used to
describe concentration
in liquids or gases,
e.g., 10,000 ppm is
approximately equivalent
to 10 g/liter or a 1%
W/V solution.
PPM (Parts Per Million)
The most common measure
of dissolved ionized
impurities in water.
It is the same as milligrams
per liter. For discussion
of ppm as a measure
of Total Ionized Solids
see Milliequivalent.
PQ (Performance Qualification)
Documented evidence
that a process or system
consistently and reproducibly
performs as intended
and does what it purports
to do. This accomplished
through extended time
studies or process runs
with simulated products
or conditions.
Precipitate
An insoluble reaction
product. When a solution
reaches saturation,
solute will begin to
come out of solution,
as when water precipitates
from the air as rain,
or calcium carbonate
precipitates out of
water to form scale,
the chalky white substance
deposited on the inside
of tea kettles.
Precommission
Preparing the plant
for commissioning (start-up).
This includes briefly
starting (bumping) all
pieces of equipment,
verifying their shaft
rotation is correct,
verifying that valves,
gauges, and other inline
devices are installed
in the correct orientation,
and performing functionality
runs on all equipment
and material. This also
includes leak tests.
Predicate Rules
A previously published
set of rules (such as
GLPs, GCP, or cGMPs)
that mandate what records
must be maintained,
the required contents
of those records, whether
signatures are necessary,
and how long the record
must be maintained.
Prefilter
A filter to trap gross
particulates located
upstream before a HEPA
filter. The efficiency
of initial prefilters
is usually in the 20%
to 30% range by the
ASHRAE Atmospheric Dust
Spot Efficiency, while
intermediate prefilters
usually have a collection
efficiency of 80% to
90% by the same test.
Preservative
A bacteriostatic or
bacteriocidal agent
added to some multiple
dose parenterals and
most cosmetics. Examples
are benzalkonium chloride
(BAC), formaldehyde,
and thimerosol (merthiolate).
Pressure Rating
Pressure at which a
system is designed to
operate, allowing for
applicable safety factors.
Pressure Vessel
A closed vessel designed
to operate at pressures
above 15 psig (103.4
kPa).
Pretreatment
Initial water treatment
steps performed prior
to final processing
to prolong the life
of cartridges and filters
and to protect downstream
elements from premature
failure.
Primary Air
Air circulating through
HEPA filters used to
produce unidirectional
flow in critical zones.
Primary Containment
The first level of containment,
consisting of the inside
portion of that container
which comes into immediate
contact on its inner
surface with the material
being contained.
Primer
Short preexisting polynucleotide
chain to which DNA polymerase
can add new deoxyribonucleotides.
Principle of Nonrepudiation
The ability to say with
confident assurance
that only one user entered
specific data or performed
specific actions on
a computer system and
that the particular
user is identifiable.
If more than one user
can get into the system
in such a way that the
audit trail cannot specify
who performed what action,
the principle of nonrepudiation
has been violated.
Prions
Virus-like proteinaceous
infectious agents. Prions
differ from viruses
in that they are not
known to contain either
DNA or RNA.
Probe
Single stranded DNA
or RNA molecules of
specific base sequence,
labeled either radioactively
or immunologically,
that are used to detect
the complementary base
sequence by hybridization.
Procedures
A documented description
of the operations to
be carried out, the
precautions to be taken
and measures to be applied
directly or indirectly
related to the manufacture
of an intermediate or
API.
Process Aids
Materials, excluding
solvents, used as an
aid in the manufacture
of an intermediate or
API (Active Pharmaceutical
Ingredient) which themselves
do not participate in
a chemical or biological
reaction (e.g. filter
aid, activated carbon,
etc.).
Process Control
Process Limits
Environmental limits
that, if exceeded, may
affect product quality
adversely.
Process Suitability
The established capacity
of the manufacturing
process to produce effective
and reproducible results
consistently.
Process Support Systems
Systems that do not
contact product and
are generally engineering
systems.
Process Systems
Systems that may contact
the drug substance or
could otherwise directly
impact product quality.
Process Validation
Establishing, through
documented evidence,
a high degree of assurance
that a specific process
will consistently produce
a product that meets
its predetermined specifications
and quality characteristics.
Process Validation
Protocol
Documented plan for
testing a pharmaceutical
product and process
to confirm that the
production process used
to manufacture the product
performs as intended.
This includes a review
of process variables
and operational limitations
as well as providing
the sampling plan under
actual use conditions.
Product Campaign
The production of more
than one product in
a facility, with strict
adherence to accepted
cleaning procedures
between these products.
The products may be
run in the same equipment,
but not at the same
time.
Product Contact Surface
A surface that contacts
raw materials, process
materials, and/or product.
Product Mix
The types and number
of different products
produced in a facility.
Product Water
The water produced as
a result of a treatment
process.
Production
All operations involved
in the preparation of
an API (Active Pharmaceutical
Ingredient), from receipt
of materials, through
processing and packaging,
to its completion as
a finished API.
Prokaryote
A unicellular organism
having a less complex
structure than a eukaryote.
It is characterized
by the absence of a
nucleus and by having
the genetic material
in the form of simple
filaments of DNA. The
sizes of most prokaryotes
vary from 0.5µm to 3µm
in equivalent radius.
Different species have
different shapes such
as spherical or Coccus
(for example, Staphylococci),
cylindrical or bacillus
(E. coli), or spiral
or spirillum (Rhodospirillum).
Promoter
A site on DNA to which
RNA polymerase will
bind and initiate transcription.
Prophylactic Surgery
Surgery to remove tissue
that is in danger of
becoming cancerous,
before cancer has the
chance to develop. Surgery
to remove the breasts
of women at high risk
of developing breast
cancer is known as prophylactic
mastectomy.
Prophylaxis
The prevention of, or
protective treatment
for disease.
Propylene Glycol
A common solvent for
antibiotics, particularly
the tetracyclines. Miscible
(soluble) in water,
but often filtered as
pure propylene glycol
prior to combination
with the antibiotic.
Its high viscosity controls
absorption of the dissolved
drug.
Prospective Validation
Establishing documented
evidence that a system
does what it purports
to do based on a preplanned
protocol.
Prosthetic Groups
Organic and/or inorganic
components other than
amino acids, contained
in proteins.
Protease
A proteolytic enzyme;
a protein that can cleave
other proteins into
smaller fragments.
Protein
One of a group of substances
constituting the greater
part of the nitrogen-containing
components of animal
and vegetable tissues.
They are of very complex
constitution, all containing
carbon, hydrogen, nitrogen,
and oxygen and some
containing in addition
iron, phosphorous, or
sulfur; chemically they
are regarded as peptides
(polypeptides) or combinations
of amino acids and their
derivatives. They are
colorless, odorless,
generally tasteless,
and of varying degrees
of solubility; they
are putrefiable and
readily undergo chemical
change, hydrolysis,
under the influence
of ferments and on boiling
with dilute acids or
alkalis.
Protein Sequencer
An instrument that will
determine the sequence
of amino acids, which
make up a particular
protein.
Proteolysis
Protein hydrolysis,
the decomposition of
protein.
Proteolytic Enzyme
(Protease)
Any enzyme that takes
part in the breaking
down of proteins. A
system of several such
enzymes is necessary
to break down proteins
to their constituent
amino acids.
Proteomics
A concept more than
a defined technology,
it refers to any protein-based
approach that has the
capacity to provide
new information about
proteins on a genomewide
scale. 75% of the predicted
proteins in multicellular
organisms have no known
cellular function.
Protocol
A prospective plan,
that when executed as
intended, produces documented
evidence that a Process
or System has been properly
qualified.
Protoplasm
A semifluid, viscous,
translucent mixture
of water, proteins,
lipids, carbohydrates,
and inorganic salts
found in all plant and
animal cells.
Protozoa
Nucleated microorganisms,
some of which are large
enough to be detected
with the naked eye.
They consist of a single
cell and or an aggregation
of nondifferentiated
cells loosely held together
and not forming tissues.
The protozoa are divided
into four classes: Sarcodina,
Mastigophora, Sporozoa,
and Infusoria (Ciliata).
Proven Acceptable Range
Psychrophile
An organism that requires
temperatures below 20°C
(68°F) for growth.
Psychrometer
A hygrometer that uses
the difference in readings
between two thermometers,
one having a wet bulb
ventilated to cause
evaporation and the
other having a dry bulb,
as a measure of atmospheric
moisture.
Psychrometry
Determination of the
properties of gas-vapor
mixtures. The air-water
vapor system is by far
the one most commonly
encountered.
Pseudonomas Diminuta
The bacterium used for
validation of sterilizing
filters. Recognized
as the challenge organism
for 0.2µm filters, its
size is 0.3 x 0.8µm
approximately. According
to the HIMA (Health
Industries Manufacturers
Association) standard,
filters must be successfully
challenged to a titre
of 107 per cm² to be
validated as sterilizing
grade 0.2µm rated.
PTFE (Polytetrafluoroethylene)
Teflon®
A fluoroplastic that
is resistant to practically
every known chemical
or solvent in combination
with the highest useful
temperature limit of
commercially available
plastics. PTFE has a
melt point of 620°F
(327°C), a useful temperature
range from -436°F (-260°C)
to 500°F (260°C), high
impact strength, and
exceptionally low coefficient
of friction. Usual processing
techniques like injection
molding are not possible
with PTFE due to a very
high molecular weight
which results in a melt
viscosity about 1 million
times higher than is
acceptable for conventional
thermoplastics. PTFE
resin is pressed into
shapes under high pressure
at room temperature
and then heated to 700°F
(371°C) to complete
the molding (sintering
process) and adjust
the crystalline content.
Public Key Certificate
(PKC)
A data file issued by
a certified authority
to a person or company
that acquires a digital
signature service. The
certificate includes
information identifying
the subject, the issuing
authority, and the period
of validity, and it
provides the related
public key. The certified
authority signs the
PKC digitally.
Pure Culture
A culture containing
only one species of
microorganism.
Pure Steam
Steam that is produced
by a steam generator
which, when condensed,
meets requirements for
WFI.
Purification
The removal of impurities
of concern. The term
has one meaning when
applied to the preparation
of drinking water, another
when applied to reagent
grade water for the
laboratory, and still
another when applied
to water used to rinse
ICs (Integrated Circuit
devices).
Purified Water, U.S.P.
Water rendered suitable
for pharmaceutical purposes
by processes such as
distillation, ion-exchange
treatment (deionization
or demineralization),
or reverse osmosis.
It meets rigid specifications
for chemical purity,
the requirements of
the Federal Environmental
Protection Agency (EPA)
with respect to drinking
water, and it contains
no added substances.
Cannot be used as raw
material for parenterals.
Common uses are: a rinse
for equipment, vials,
and ampoules, and as
make up for cosmetics,
bulk chemicals, and
oral products. For FDA
acceptance, purified
water must contain less
than 0.5 mg/l of TOC
(Total Organic Carbon),
and less than 100 CFU
(Colony Forming Units).
Purine
A nitrogen-containing,
double-ring, basic compound
that occurs in nucleic
acids. The purines in
DNA and RNA are adenine
and guanine.
Purity
The ratio of desirable
to undesirable components
in a liquid as determined
on a weight basis per
unit volume of sample.
PVC (Polyvinyl Chloride)
The largest volume of
the vinyl family of
plastics. Overall it
has excellent basic
properties, may be easily
processed and welded,
and is exceptionally
economical in cost.
Homopolymers grades
of PVC comprise over
80% of all PVC used,
and contain 56.8% chlorine
by weight. When the
chlorine content is
increased to about 67%
its heat deflection
temperature at 264 psi
increases from 155°F
(68°C) to 218°F (103°C).
Because PVC is a thermally
sensitive thermoplastic
compounding ingredients
such as heat stabilizers,
lubricants, fillers,
plasticizers, impact
modifiers, pigments,
and processing aids
must be added to make
it processible. PVC
is prone to produce
extractables during
start-up in high purity
water.
PVDF (Polyvinylidene
Fluoride) Kynar®, Sygef®,
Solef®
A thermoplastic fluoropolymer
with a melt point of
352°F (178°C), and a
wide service range from
-40°F (-40°C) to 284°F
(140°C). It has a very
linear chemical structure,
and is similar to PTFE
with the exception of
not being fully fluorinated,
i.e. having 3% hydrogen
by weight. Its drawbacks
in the area of chemical
resistance include unsuitability
with strong alkalis,
fuming acids, polar
solvents, amines, ketones,
and esters. It has a
high tensile strength
as well as a high heat
deflection temperature.
It is readily weldable,
offers high purity qualities,
and is resistant to
permeation of gases.
PVDF is a relatively
inert material and contributes
little in the way of
contamination to pharmaceutical
water.
Pyrimidine
A nitrogen-containing,
single ring, basic compound
that occurs in nucleic
acids. The pyrimidines
in DNA are cytosine
and thymine, in RNA,
cytosine, and uracil.
(also see: Purine)
Pyrogen A foreign substance
that produces a fever
response in humans and
animals, hence the name
pyrogen (heat producing).
Chemically, the lipopolysaccharide
outer layer of gram-negative
bacteria. Bacterial
pyrogens were at one
time believed to be
toxic substances released
when bacterial cells
disintegrate and are
therefore still referred
to as endotoxins. Parenteral
drugs must be essentially
pyrogen free. (also
see; Lipopolysaccharide
(LPS), Endotoxin) Pyrophoric
A chemical that will
spontaneously ignite
in air at or below a
temperature of 130°F
(54.5°C).
Q
QA (Quality Assurance)
The sum total of the
organized arrangements
made to ensure that
all APIs (Active Pharmaceutical
Ingredients) are of
the quality required
for their intended use
and that quality systems
are maintained.
QC (Quality Control)
Checking or testing,
that specifications
are met, or the regulatory
process through which
the industry measures
actual quality performance,
compares it with standards,
and acts on the difference.
Qualification
Action of providing
that equipment or ancillary
systems are properly
installed, work correctly,
and actually lead to
the expected results.
Qualification is part
of validation, but the
individual qualification
steps alone do not constitute
process validation.
Quality Assurance (QA)
Group
The group who interprets
the GMP regulations
and guidelines.
Quality Control (QC)
Group
The group who enforces
the GMP regulations.
Quality Unit(s)
An organizational unit
independent of production
that fulfills both Quality
Assurance and Quality
Control responsibilities.
This may be in the form
of separate QA and QC
units, a single individual
(or group), depending
upon the size and structure
of the organization.
Quality Function
The entire collection
of activities from which
the industry achieves
fitness for use, no
matter where these activities
are performed.
Quarantine
The status of materials
isolated physically
or by other effective
means pending a decision
on their subsequent
approval or rejection.
Quick Stop
DNA mutants of E. coli
cease replication immediately
when the temperature
is increased to 42°C.
R
Radiation Sterilization
Sterilization using
gamma radiation emitted
from radioactive materials
such as cobalt-60, or
cesium 137. If proper
dosage of nuclear radiation
can be documented, sterility
testing is not required.
Radio-Immunoassay (RIA)
A highly sensitive method
of detecting and measuring
the concentration of
biological compounds
in vivo.
Radioactive Material
A material or combination
of materials that spontaneously
emits ionizing radiation.
Raw Material
A general term used
to denote starting materials,
reagents, intermediates,
process aids, and solvents
intended for use in
the production of intermediates
or APIs (Active Pharmaceutical
Ingredients).
rDNA (Recombinant DNA)
The hybrid DNA produced
by joining pieces of
DNA from different sources.
Reagent
A substance used (as
in detecting or measuring
a component, in preparing
a product, or in developing
photographs) because
of its chemical or biological
activity.
Reagent Grade Water
Water suitable for use
in making up reagents
or for use in sensitive
analytical procedures.
There are several grades
of reagent grade water
as defined by various
professional organizations,
such as ASTM, CAP, NCCLS,
and ACS:
1. Type I: Used for
procedures requiring
maximum accuracy and
precision, such as atomic
spectrometry, flame
photometry, enzymology,
blood gas, pH and specific
ion determinations;
reference buffer solutions;
and reconstitution of
lyophilized materials
used as standards. ASTM
to produce Type I water
specifies distillation
pretreatment of feedwater.
2. Type II: Recommended
for most analytical
or general laboratory
testing such as hematological,
seralogical, and microbiological
procedures as well as
chemical methods not
specifically stated
or proven to require
Type I quality. ASTM
specifies preparation
of Type II by distillation
and recommends it whenever
freedom from organic
impurities is important.
3. Type III: Satisfactory
for some general laboratory
tests; for most qualitative
analyses such as urinalysis,
parasitology, and histological
procedures; for rinsing
of analytical samples;
preparation of stock
solutions; and for washing
or rinsing of glassware
(final glassware rinsing
should be performed
with the water type
specified for the procedure
performed). Distillation,
mixed-bed deionization,
and reverse osmosis
(with high quality feedwater)
can be used to generate
Type III.
Recalcification
A technique producing
serum from anticoagulated
plasma. Citrate and
oxalate act as anticoagulants
because they are Ca++
(Calcium Ion) chelating
agents; Ca++ as calcium
chloride is added in
excess (1/40 Molar).
Ca++ is a coagulation
co-factor (catalyst)
and promotes clot formation.
Recessive Allele
A gene that is expressed
only when its counterpart
allele on the matching
chromosome is also recessive
(not dominant). Autosomal
recessive disorders
develop in persons who
receive two copies of
the mutant gene, one
from each parent who
is a carrier.
Recirculation
Continuous recirculation
may be necessary to
maintain uniformly high
purity in larger water
systems. Water is continuously
recirculated and reprocessed
to prevent stagnation
and to rinse out residual
impurities in the system.
Bacteria flourish in
stagnant water, especially
if temperature is conducive
to growth.
Recombinant
Pertaining to the recombining
of generic material
from one species into
alternate sequences.
Plasmids may then be
used to incorporate
the genetic material
into other organisms
such as E. coli bacteria.
Recombinant Clone
Clone containing recombinant
DNA molecules.
Recombinant DNA Molecules
In the context of the
NIH Guidelines, recombinant
DNA molecules are those
constructed outside
living cells by joining
natural or synthetic
DNA segments to DNA
molecules that can replicate
in a living cell, or
molecules that result
from the replication
of those described above.
Recombinant DNA (rDNA)
The hybrid DNA produced
by joining pieces of
DNA from different sources.
Recombinant DNA Techniques
Procedures that transfer
genetic material between
organisms or species.
Recombinant DNA Technology
Procedure used to join
together DNA segments
in a cell-free system
(an environment outside
a cell or organism).
Under appropriate conditions,
a recombinant DNA molecule
can enter a cell and
replicate there, either
autonomously or after
it has become integrated
into a cellular chromosome.
Recombination
The process by which
progeny derive a combination
of genes different from
that of either parent.
In higher organisms,
this can occur by crossing
over.
Recovery
Any treatment of materials
by a process intended
to make them suitable
for further use.
Recovery Time
The time after an upset
in a room's HVAC environmental
parameters for the room
to return to "normal"
conditions, such as
a return to acceptable
humidity levels after
a room wash down. This
occurs within a certain
number of air changes
after the upset source
is removed, minimally
six to ten, depending
on the severity of the
upset, the quality of
the air supply, and
the degree of mixing
of room air.
Reference Standard,
Primary
A substance that has
been shown by an extensive
set of analytical tests,
to be authentic material
of high purity. This
standard may be obtained
from a recognized source
or may be prepared by
independent synthesis
or by further purification
of existing production
material.
Reference Standard,
Secondary A substance
of established quality
and purity, as shown
by comparison to a primary
reference standard,
used as a reference
standard for routine
laboratory analysis.
Referential Integrity
Relationship between
records that ensures
data integrity by maintaining
unbreakable links between
related electronic records.
It ensures confidence
that a specific record
(such as a calculated
chromatographic result)
is unmodified, unmanipulated,
and otherwise uncorrupted
after its creation and
that still carries the
references to the other
electronic records that
were used to generate
it.
Refrigerants
Fluids used for heat
transfer in a refrigerating
system; the refrigerant
absorbs heat and transfers
it at a higher temperature
and higher pressure,
usually with a change
of state. Refrigerants
can be: 1. Primary refrigerants.
Liquids with low boiling
points that change from
a liquid to a gas after
absorbing heat. 2. Secondary
refrigerants. Substances
that act only as heat
carriers, such as brine,
air, and water.
Regenerate
Restore ion exchange
of resins by reversing
the process. An acid
rinse is used to restore
cation resin capacity
and a sodium hydroxide
rinse is used to restore
anion resin capacity.
Regulatory Affairs
Drug companies must
show that their products
consistently meet standards
set by government agencies.
Regulatory affairs departments
document those activities,
submit proposals, and
follow those proposals
through completion or
approval.
Regulatory Region or
Sequence
A DNA base sequence
that controls gene expression.
Reject Stream
In reverse osmosis and
ultrafiltration, those
impurities not able
to permeate the membrane
are said to be rejected
(removed). They are
flushed away in the
reject (waste) stream.
Relational Database
Management System (RDBMS)
A type of database system
that stores data in
related tables. A relational
database is powerful
because it does not
assume how data are
related or how they
will be extracted from
the database. As a result,
the same database can
be viewed in many different
ways.
Relative Humidity (%
RH)
The ratio (measured
in percent) of actual
water vapor pressure
in air to the pressure
of saturated water vapor
in air at the same temperature
and pressure.
Release
The discharge of a microbiological
agent or eukaryotic
cell from a containment
system.
Renaturation
The restoration of biological
activity to a denatured
protein or nucleic acid.
The strands of a DNA
duplex, for example,
are denatured at high
temperatures but can
be correctly reformed
by a slow cooling.
Representative Sample
A sample that consists
of a number of units
that are drawn based
on rational criteria
such as random sampling
and intended to assure
that the sample accurately
portraits the material
being sampled.
Reproductive Toxicology
Studies of whether exposure
affects male or female
fertility.
Reprocessing
A system of reworking
batches that do not
conform to standards
or specifications, including
"the steps taken
to ensure that the reprocessed
batches will conform
to all established standards,
specifications, and
characteristics".
Reprocessing (ICH API
definition)
Introducing an intermediate
or API, including that
which does not conform
to standards or specifications,
back into the process
and repeating a crystallization
step or other appropriate
chemical or physical
manipulation steps (e.g.,
distillation, filtration,
chromatography, milling,
etc.) that are part
of the established manufacturing
process. Continuation
of a chemical reaction
after an in-process
control test shows the
reaction to be incomplete
is considered to be
part of the normal process,
and not reprocessing.
Resin
Ion exchange resins
are usually bead-like
spherical materials
with an affinity for
particular ions. Cation
exchange resins made
of styrene and divinylbenzene
containing sulfonic
acid groups will exchange
hydrogen ions for any
cations they encounter.
Similarly, anion exchange
resins made of styrene
and divinylbenzene containing
quaternary ammonium
groups will exchange
a hydroxyl ion for any
anions.
Resistance (Filter)
The pressure drop across
a filter at a stated
flow and under given
conditions; generally
expressed in millimeters
water gauge or PSI,
or in SI units as N/m²
or Pascals.
Resistivity The reciprocal
of conductivity (R=1/C).
A measure of specific
resistance to the flow
of electricity. In water,
provides an easy mean
of continuously measuring
the purity of very low
Total Dissolved Solids
(TDS), or ionic concentration.
The fewer the dissolved
ions in water, the higher
its resistivity. Resistivity
is normally expressed
in Megohm-cm and is
equivalent to one million
ohms of resistance measured
between two electrodes
one centimeter apart.
The theoretical maximum
ionic purity of water
is 18.3 Megohm-cm at
25°C.
Resolution
Degree of molecular
detail on a physical
map of DNA, ranging
from low to high.
Restriction Enzyme,
Endonuclease A protein
that recognizes specific,
short nucleotide sequences
and cuts DNA at those
sites. Bacteria contain
over 400 such enzymes
that recognize and cut
over 100 different DNA
sequences.
Restriction Enzyme Cutting
Site
A specific nucleotide
sequence of DNA at which
a particular restriction
enzyme cuts the DNA.
Some sites occur frequently
in DNA (e.g., every
several hundred base
pairs), others much
less frequently (rarecutter;
e.g., every 10,000 base
pairs).
Restriction Fragment
Length Polymorphism
(RFLP)
Variation between individuals
in DNA fragments sizes
cut by specific restriction
enzymes; polymorphic
sequences that result
in RFLPs are used as
markers on both physical
maps and genetic linkage
maps. RFLPs are usually
caused by mutation at
a cutting site.
Retest Date
The date when samples
of the API (Active Pharmaceutical
Ingredient)a material
should be re-examined
to ensure that material
is still suitable for
use.
Retinoblastoma
An eye cancer caused
by the loss of a pair
of tumor-suppressor
genes; the inherited
form typically appears
in childhood, since
one gene is missing
from the time of birth.
Retrospective Validation
Establishing documented
evidence that a system
does what it purports
to do based on review
and analysis of historic
information.
Retrovirus
An oncogenic, RNA-containing
virus, which replicates
through a double-stranded
DNA intermediate necessitating
the presence of an RNA-dependent
DNA polymerase.
Revalidation
Repetition of validation
process or a specific
portion of it.
Revalidation
Extent of validation
necessary to assure
that changes made to
qualified or validated
equipment, utilities,
systems and process
do not adversely affect
the finished product.
Implemented changes
should be tracked and
evaluated through a
thorough, dynamic, change
control program.
Reverse Osmosis (RO)
The reversal of osmosis
to purify water. In
osmosis, water diffuses
through a semipermeable
membrane from a region
of higher concentration
(such as pure fresh
water) into one of lower
concentration (such
as a solution of water
and salt). The flow
of water can be reversed
with an opposing pressure
that exceeds osmotic
pressure. With RO, water
is forced out of the
lower concentrated solution
(such as the salt solution),
leaving the solute (impurities)
behind.
Reverse Osmosis (RO)
RO is one of two acceptable
techniques for producing
Water For injection
(WFI), U.S.P. Procedure
involves passing purified
water across a semipermeable
membrane against an
osmotic gradient. R.O.
is an excellent pretreatment
for deionized water
that will be subsequently
filtered, because silt
and colloids are removed.
Usual performance of
R.O. is removal of organics,
multi-valent ions, and
90% of mono-valent ions.
Reworking
Subjecting an intermediate
or API (Active Pharmaceutical
Ingredient) that does
not conform to standards
or specifications, to
one or more processing
steps that are different
from the established
manufacturing process
so that its quality
may be made acceptable
(e.g., recrystallizing
with a different solvent).
A molecule consisting
of a number of ribonucleotides
attached together to
form a long strand one
nucleotide thick. Each
nucleotide contains
the sugar, ribose, and
one of four different
bases: cytosine, adenine
and guanine (as in DNA)
and uracil (as opposed
to thymine in DNA).
The major portion of
cellular RNA occurs
as ribosomal RNA (rRNA),
to a lesser extent as
transfer RNA (tRNA)
and less still as messenger
RNA (mRNA), all three
forms being concerned
with transformation
of the DNA sequence
into the complementary
protein sequence. It
also occurs in some
viruses where it acts
as the hereditary material.
Ribonucleotide
Ribosomal RNA (rRNA)
A class of RNA found
in the ribosomes of
cells.
Ribosomes
Small cellular components
composed of specialized
ribosomal RNA and protein;
site of protein synthesis.
Rickettsias
Gram-negative microorganisms
that are often carried
by arthropod vectors
and may infect humans
and other mammals. Generally
smaller than other bacteria,
they require living
cells for growth.
Rinse
The operation that follows
regeneration, a flushing
out of excess regenerant
solution.
Roller Bottles
Small cylindrical bottles
often used as bioreactors
in the production of
products by cell culture.
The bottles are kept
on a device that rotates
them slowly to help
assure proper growth.
Automated systems may
also be used for large
arrays of roller bottles
introducing sterile
media and harvesting
finished product automatically.
Rouge
Form of surface corrosion
that occurs in some
stainless steel piping
systems.
Roughness
Consists of the finer
irregularities of the
surface texture, usually
including those irregularities
that result from the
manufacturing process.
These are considered
to include traverse
feed marks and other
irregularities within
the limits of the roughness
sampling length.
S
Saccharomyces Cerevisiae
Better known as beer
yeast, ordinary yeast.
Yeast used in rDNA research.
Safranin
A base, obtained from
aniline; aniline pink;
used as a stain in histology.
Salinity
The concentration of
soluble minerals (mainly
salts of the alkali
metals or of magnesium)
in water.
Salmonella
A large genus of the
tribe Salmonellae, family
Enterobacteriaceae,
containing motile, gram-negative,
rod-shaped organisms
that ferment dextrose,
forming acid and usually
gas. Several species
occur as intestinal
pathogens in acute inflammations
in humans and domestic
animals. Salmonella
typhimurium causes food
poisoning in humans.
Salt
A compound formed by
the interaction of an
acid and a base, the
hydrogen atoms of the
acid being replaced
by another positive
ion derived from the
base.
Salt Rejection
In reverse osmosis,
the ratio of salts removed
(rejected) to the original
salt concentration.
"Salvage"
Plasma
Plasma obtained by centrifugation
of outdated (older than
21 days) whole blood.
This type of plasma
is difficult to convert
to serum because most
coagulation factors
have lost their activity
Sanitization
That part of decontamination
that reduces viable
microorganisms to a
defined acceptance level,
normally achieved by
using a chemical agent
or heat.
Saponification
Alkaline hydrolysis
of triacyl glycerols
to yield fatty acids
as soaps.
Sarcoma
A type of cancer that
starts in bone or muscle.
Saturated Air
When there is a state
of mutual equilibrium
between the moist air
and the liquid or solid
phases of water. Saturated
air holds as much water
vapor as it can for
a given temperature
and pressure.
Saturated Fatty Acids
Fatty acids containing
fully saturated alkyl
chains.
Saturation Humidity
The air is saturated
when the partial pressure
of water vapor in the
air at a given temperature
equals the vapor pressure
of water at the same
temperature.
Saturation Index
The relation of calcium
carbonate to the pH,
alkalinity, and hardness
of water to determine
its scale-forming tendency.
Scale
The mineral deposit
that can coat the insides
of boilers or the surfaces
of RO membranes. It
consists mainly of calcium
carbonate that precipitates
out of solution under
certain conditions of
pH, alkalinity, and
hardness.
Scale-up
To take a biopharmaceutical
manufacturing process
from the laboratory
scale to a scale at
which it is commercially
feasible.
Scratch
An elongated mar in
the metal's surface
not associated with
the predominant surface
texture pattern, which
is visible to the unaided
eye.
SDR
Secondary Containment
Level of containment
that is external to
and separate from primary
containment.
Secure Retention
The ability to generate
accurate and complete
copies of records in
both human-readable
and electronic form
suitable for inspection,
review, and copying
by FDA. Records must
be protected to enable
their accurate and ready
retrieval through the
records retention period.
Seed Lot
Seed Lot System - A
seed lot system is a
system according to
which successive batches
of a product are derived
from the same master
seed lot at a given
passage level. For routine
production, a working
seed lot is prepared
from the master seed
lot. The final product
is derived from the
working seed lot and
has not undergone more
passages from the master
seed lot than the vaccine
shown in clinical studies
to be satisfactory with
respect to safety and
efficacy. The origin
and the passage history
of the master seed lot
and the working seed
lot are recorded.
Master Seed Lot -
A culture of a microorganism
distributed from a single
bulk into containers
in a single operation
in such a manner as
to ensure uniformity,
to prevent contamination
and to ensure stability.
A master seed lot in
liquid form is usually
stored at or below -70ºC.
A freeze-dried master
seed lot is stored at
a temperature known
to ensure stability.
Working Seed Lot - A
culture of microorganism
derived from the master
seed lot and intended
for use in production.
Working seed lots are
distributed into containers
and stored as described
above for master seed
lots.
Seed Stock
The initial inoculum,
or the cells placed
in growth medium from
which other cells will
grow.
Seed Tank Industrial
fermentations are generally
started in tanks smaller
than a 1,000 to 50,000
gallon main fermenter.
This small "seed"
tank may be up to 100
gallons and propagate
enough organisms to
"kick-off"
the main fermentation.
Often, a seed tank may
be large enough to require
its own seed tank.
Sedimentation
A primary step in municipal
water treatment. Water
is allowed to stand
long enough for solids
to settle by gravity.
Also called settling.
Segregated
Storage in the same
room or inside area,
but physically separated
by distance from incompatible
materials.
SEM (Scanning Electron
Microscopy)
Utilizes an electron
beam to produce images
over a very broad magnification
range of 10X to 105X.
The technique is somewhat
limited by the conductivity
of the material but
works very well to inspect
316L stainless steel.
Typical magnification
levels for surface defect
evaluation are from
100 to 4,000.
Semipermeable
Membranes that do not
have measurable pores
but through which smaller
molecules can pass.
Self Draining
Capable of elimination
of all fluid from the
system due to the force
of gravity alone.
Sensible Heat (SH)
Heat that causes a change
of temperature without
causing a change of
state.
Sensible Heat Ratio
The ratio of room sensible
heat to room total heat
as expressed in the
formula: Sensible Heat
ratio (SHR) = Room Sensible
Heat (SH)/Room Total
Heat (TH)
Sensitizer
A chemical that causes
a substantial proportion
of exposed people or
animals to develop an
allergic reaction in
normal tissue after
repeated exposure to
the chemical.
Semiautomatic Arc Welding
Arc welding with equipment
that controls only the
filler metal feed. The
advance of the welding
is manually controlled.
Sepsis
The presence of various
pus-forming and other
pathogenic organisms
or their toxins in the
blood or tissues; septicemia.
Sequence Tagged Site
(STS)
Short (200 to 500 base
pairs) DNA sequence
that has a single occurrence
in the human genome
and whose location and
base sequence are known.
Detectable by polymerase
chain reaction, STSs
are useful for localizing
and orienting the mapping
and sequence data reported
from many different
laboratories and serve
as landmarks on the
developing physical
map of the human genome.
Expressed sequence tags
(ESTs) are STSs derived
from cDNAs.
Sequencing (of DNA or
RNA) Determination of
the order of nucleotides
(base sequences) in
a DNA or RNA molecule
or the order of amino
acids in a protein.
Sera
One of the plural forms
of serum.
Serratia Marcescens
They are minute, rod-shaped
or coccoid, aerobic,
gram-negative organisms,
found on various foodstuffs
as a pink or reddish
growth, nonpathogenic.
Used to validate 0.45µm
removal rated filters.
Serum
The liquid portion remaining
after clotting whole
blood or plasma.
Service Life
The life expectancy
or number of cycles
for which a processing
unit will maintain its
performance.
Sex Chromosomes
Those whose content
is different in the
two sexes - usually
labeled X and Y (or
W and Z), female sex
has XX (or WW), male
is XY (or WZ).
Shielded Metal-Arc
Welding (SMAW)
An arc welding process
that produces coalescence
of metals by heating
them with an arc between
a covered metal electrode
and the work. Shielding
is obtained from decomposition
of the electrode covering.
Pressure is not used
and filler metal is
obtained from the electrode.
Shotgun Method
Sequencing method that
involves randomly sequencing
tiny cloned pieces of
the genome, with no
foreknowledge of where
on a chromosome the
piece originally came
from. This can be contrasted
with "directed"
strategies, in which
pieces of DNA from adjacent
stretches of a chromosome
are sequenced. Direct
strategies eliminate
the need for complex
reassembly techniques.
Because there are advantages
to both strategies,
researchers expect to
use both random (or
shotgun) and directed
strategies in combination
to sequence the human
genome.
Signature (signed)
See definition for signed
Signed (signature)
(ICH API definition)
The record of who performed
a particular action
or review. This record
may be initials, full
handwritten signature,
personal seal, or authenticated
and secure electronic
signature.
Single Gene Disorder
Hereditary disorder
caused by a mutant allele
of a single gene (e.g.,
Duchenne muscular dystrophy,
retinoblastoma, sickle
cell disease).
Sickle-cell Anemia
An inherited, potentially
lethal disease in which
a defect in hemoglobin,
the oxygen-carrying
pigment in the blood,
causes distortion (sickling)
and loss of red blood
cells, producing damage
to organs throughout
the body.
Signed (signature)
The record of who performed
a particular action
or review. This record
may be initials, full
handwritten signature,
seal, or authenticated
and secure electronic
signature.
Silica Silicon
Dioxide (SiO2) and its
hydrated forms are classified
as reactive and nonreactive.
Generally, reactive
Silica is removed by
the anion exchange resin.
Reactive Silica is only
slightly ionized and
is held lightly by the
anion resin. It is for
this reason that Silica
is the first thing to
break through when the
resin nears exhaustion.
Nonreactive Silica is
generally considered
to be particulate (colloidal)
in nature.
SIP (Steam In Place)
The introduction of
steam to sanitize or
sterilize a piece of
equipment without relocating
the equipment.
Slope
An incline or deviation
from the horizontal.
A tube or pipe installed
in the horizontal plane
is said to slope if
one end is positioned
higher than the other.
Smoke Control
The use of physical
barriers and mechanical
ventilation to control
the spread of smoke
from a fire.
Smoke Purge
The use of mechanical
ventilation to remove
smoke resulting from
fire.
Smoke Test
Visualization of airflow
streams in a clean space
using artificially generated
smoke, such as Titanium
smoke, CO2, or glycol
fog.
Softener
Water treatment equipment
that uses a sodium-based
ion-exchange resin,
principally to remove
cations.
Softening
A pretreatment process
which uses cation exchange
resin to remove hardness
elements (calcium and
magnesium) from water.
The cation resin is
regenerated with Sodium
Chloride (NaCl) and
during the exchange
process, the calcium
and magnesium are removed
from the water and replaced
with sodium ions (Na+).
The resulting sodium
salts are much more
soluble and do not precipitate,
which provides better
feed water to the RO
system.
Software
An executable program
that operates on an
automated system.
Soldering
A metal joining process
wherein coalescence
is produced by heating
to suitable temperatures
and by using a nonferrous
alloy fusible at temperatures
below 427°C (800ºF)
and having a melting
point below that of
the base metals being
joined. The filler metal
is distributed between
closely fitted surfaces
of the joint by capillary
attraction. In general,
solders are lead-tin
alloys and may contain
antimony, bismuth, and
other elements.
Solid Tumors
Cancer cells which grow
as a solid mass.
Soluble Antigen
Generally used in reference
to vaccine production.
As opposed to a whole
live or attenuated virus,
a soluble antigen is
a fragment of the virus
that produces immunity.
Also refers to large
molecular weight polysaccharides
from some bacteria which
can act as vaccines.
Solute
The substance that dissolves
to form ions in solution.
Solvent
A liquid capable of
dissolving a solute.
Solvent
An inorganic or organic
liquid used as a vehicle
for the preparation
of solutions or suspensions
in the manufacture of
an intermediate or API
(Active Pharmaceutical
Ingredient).
Somatic Cell
Any cell in the body
except gametes and their
precursors.
Somoclonal Variation
Genetic variation produced
from the culture of
plant cells from a pure
breeding strain; the
source of the variation
is not known.
SOP (Standard Operating
Procedures)
The description of necessary
activities to respond
to normal and abnormal
situations in an operating
system. The SOP may
include a troubleshooting
checklist, list of personnel
to contact, etc. SOPs
should also describe
normal operation, maintenance,
and cleaning of the
system, and normal operating
parameters. An SOP may
be created for any system
but an SOP must be created
for each system requiring
qualification.
Source Code
An original computer
program either in human
readable or machine-readable
form.
Southern Blotting
Transfer by absorption
of DNA fragments separated
in electrophoretic gels
to membrane filters
for detection of specific
base sequences by radiolabeled
complementary probes.
Sparger
A device used to agitate,
oxygenate, aerate, or
add a chemical to a
liquid by means of compressed
air or gas entering
through small holes
in a pipe below the
liquid surface.
Specific Conductance
The reciprocal of specific
resistance usually expressed
in micromhos/cm.
Specific Humidity
Also known as Humidity
Ratio, and Absolute
Humidity, is the weight
of water vapor in each
pound of dry air expressed
in grains of moisture
per pound of dry air,
or pounds of moisture
per pound of dry air.
(also see: Saturation
Humidity) NOTE: 7,000
grains = 1.0 pound.
Humidity of air mixtures
is normally discussed
in terms of grains of
moisture per pound rather
than the more common
term of relative humidity
because the grains of
moisture in an air stream
do not change when it
is heated or cooled,
unless condensation
takes place.
Specific Ion Determinations
Electrochemical measurement
of trace ion levels
in solution.
Specific Resistance
The resistance of a
one-centimeter cube
of water to the passage
of electricity under
standard conditions,
expressed in ohms/cm.
A measure of the Total
Ionized Solids concentration.
Specific Volume
In Psychrometry, the
cubic feet of the mixture
per pound of dry air.
Specification
A list of testes, references
to analytical procedures,
and appropriate acceptance
criteria that are numerical
limits, ranges, or other
criteria for the test
described. It establishes
the set of criteria
to which an intermediate
or API (Active Pharmaceutical
Ingredient) should conform
to be considered acceptable
for its intended use.
"Conformance to
Specifications"
means that the intermediate
or API, when tested
according to the listed
analytical procedures,
will meet the listed
acceptance criteria.
Specificity
Exerting a definitive
and distinctive influence
on a particular part
of the body and on the
course of a particular
disease.
Spinner Flasks
Small laboratory bioreactors
used for the initial
growth of mammalian
cells lines.
Spore
A reproductive cell
or seed of algae, fungi,
or protozoa.
Spore, bacterial
A bacterial spore is
a resistant body formed
as part of the life
cycle of some bacteria.
Bacterial spores are
able to withstand severe
environmental conditions
(e.g., heat, drying,
chemicals) for many
years. When conditions
are favorable, spores
germinate into vegetative
bacterial cells capable
of replication.
Sporicide
An agent that destroys
bacterial and fungal
spores.
Spray Drying
Process by which a material
in suspension is converted
into droplets that may
be coated by a substance,
either melted or dissolved
in the droplet's media.
The action in spray
drying is primarily
that of evaporation,
energy is applied to
the droplet forcing
evaporation of the media
with both energy and
mass transfer through
the droplet. Examples
of this technology include,
pharmaceutical tablet
granulation, and rapid
drying which results
in free-flowing powders
on a continuous basis.
Spray drying process
consists of the following
steps:
1. Formation of a
slurry to be sprayed;
this slurry may be a
simple concentrated
solution or the dispersion
of an insoluble material
in a solution.
2. Liquid atomization
into droplets; this
action is critical as
the droplet size will
dictate the equipment
size as well as the
final product size.
There are four types
of atomization devices:
air, airless, disk (or
rotary) spray, and ultrasonic.
3. Exposure of the droplet
to a heated gas flow;
this gas (normally air)
supplies the energy
required to vaporize
the solvent. Collection
of the dry free-flowing
powder or encapsulated
liquid or solid.
Stability
Generally, stability
refers to the physico-chemical
condition of a parenteral,
biological, or shelf
life of labile drugs.
Certain drugs must pass
U.S.P. or CFR stability
tests. For example,
human serum albumin
must pass certain limits
of nephelometric turbidity.
Also manufacturers must
have documentation of
potency of labile products
under labeled storage
conditions.
Stability Index
An empirical modification
of the saturation index
used to predict scaling
or corrosive tendencies
in water systems.
Stainless Steel
There are more than
70 standard types of
stainless steel and
many special alloys.
These steels are produced
in the wrought form
(AISI types) and as
cast alloys (ACI types).
Generally, all are iron
based, with 12 to 30
percent chromium, 0
to 22 percent nickel,
and minor amounts of
carbon, columbium, copper,
molybdenum, selenium,
tantalum, and titanium.
There are three groups
of wrought stainless
steels:
1. Martensitic Alloys:
characteristically magnetic
and hardenable by heat
treatment are oxidation
resistant. They are
exemplified by Type
410 (UNS S41000). Contain
12 to 20 percent chromium
with controlled amount
of carbon and other
additives. Their corrosion
resistance is inferior
to austenitic stainless
steels, and is generally
used in mildly corrosive
environments and for
cutlery, turbine blades,
and high-temperature
parts.
2. Ferritic Stainless:
characteristically magnetic
but not hardenable by
heat treatment. Contain
15 to as much as 30
percent Cr with low
carbon content (0.1
percent). The higher
chromium content improves
its corrosive resistance.
Type 430 (UNS S43000)
widely used in nitric
acid plants is a typical
example. Corrosion resistance
is rated good, although
ferritic alloys are
not good against reducing
acids such as HCl.
3. Austenitic Stainless:
widely used in bioprocessing,
are characteristically
non-magnetic, not hardenable
by heat treatment, and
are the most corrosion
resistant of the three
groups. These steels
contain 16 to 26 percent
chromium, 6 to 22 percent
nickel. Carbon is kept
low (0.08 percent) to
minimize carbide precipitation.
To avoid precipitation,
special stainless steels
stabilized with titanium,
columbium, or tantalum,
have been developed
(types 321, 347, 348).
Another approach to
the problem is the use
of low-carbon steels
such as 304L and 316L,
with 0.03 percent maximum
carbon. Type 302 is
the basic alloy of this
group. Types 304 (UNS
S30400) and 304L are
low-carbon versions
of 302. Types 316 (UNS
S31600), 316L, and 317
(UNS S31700), with 2.5
to 3.5 percent molybdenum,
are the most corrosion
resistance.
Cast Stainless Alloys:
are widely used in pumps,
valves, and fittings.
All corrosion resistant
alloys have the letter
C plus a second letter
(A to N) denoting increasing
nickel content. Numerals
indicate maximum carbon.
Typical members of this
group are CF-8, similar
to 304 stainless, CF-8M,
similar to 316, and
CD-4M Cu, which has
improved resistance
to nitric, sulfuric,
and phosphoric acids.
Standard Atmospheric
Conditions
At sea level these conditions
are: 1. Temperature
- 59°F. 2. Pressure
- 29.921 Inches of mercury
3. Density - 0.0765
lbs dry air/cubic foot
Standard Dimensional
Ratio (SDR)
The most commonly accepted
means for providing
a pipe wall thickness
category and constant
mechanical properties
for many plastic materials.
Used for solid, homogeneous
pipe, the SDR is found
by dividing the average
outside diameter of
a pipe by the wall thickness.
Standard Operating
Procedures
Standpipe System
A wet or dry system
of piping, valves, outlets,
and related equipment
designed to provide
water at specified pressures
and installed exclusively
for the fighting of
fires.
Start-Up
The initial operation
of equipment to prove
that it is installed
properly and operates
as intended. Start-Up
is considered complete
when the selected equipment
will adequately process
product as specified.
State of Control
A condition in which
all operating variables
that affect performance
remain within such ranges
that the system or process
performs consistently
and as intended.
Statistical Process
Control (SPC)
A process control method
to demonstrate mathematically
that a process or system
is operating within
the limitations established
for the parameter(s)
in question.
Steam In Place (also
see: SIP)
Sterile Absence of life;
usually refers to absence
of viable microorganisms.
Sterile Water
For Injection, U.S.P.
A form in which water
is distributed in sterile
packages. Sterile Water
for Injection is intended
mainly for use as a
solvent for parenteral
products such as sterile
solids that must be
distributed dry because
of limited stability
of their solutions.
It must be packaged
only in single-dose
containers of not larger
than 1-liter size.
Sterile Water for Irrigation,
U.S.P.
This form of water meets
most, but not all, of
the requirements for
Sterile Water for Injection.
The exceptions are with
respect of container
size (i.e., the container
may contain a volume
of more than 1 liter),
container design (i.e.,
the container may be
designed so as to empty
rapidly the contents
as a single dose), particulate
matter requirements
(i.e., need not meet
the requirement for
Large Volume Injections
for single-dose infusions),
and labeling requirements
(e.g., the designation
"For Irrigation
Only" and "Not
For Injection"
appear prominently on
the label).
Sterile Engineering
Design (Fermentation)
The application of techniques
to prevent contamination
of a fermentation process
by undesirable organisms.
It includes three basic
phases relating to the
operation of the plant.
First, the fermenter
with the ancillary equipment,
pipework, and valves
must be brought to a
sterile state. Secondly,
the fermenter feed must
be sterilized, and finally,
sterile barriers at
the interface between
the fermenter and the
outside environment
must be maintained.
Sterilization
The act or process,
physical or chemical,
that destroys or eliminates
all viable microbes
including resistant
bacterial spores from
a fluid or a solid.
Despite being stated
as an absolute, the
action of sterilization
is usually stated in
terms of probability.
Examples of sterilization
methods are: steam treatment
at 121°C, dry heat at
450°F, flushing with
a sterilizing solution
such as Hydrogen Peroxide
(H2O2) or ozone (O3),
irradiation, and filtration.
Sterilizing Filter
A filter that, when
challenged with the
microorganisms Brevundimonas
diminuta, at a minimum
concentration of 107
organisms per square
centimeter of filter
surface, produces a
sterile effluent.
Steroids
Classified as lipids,
naturally occurring
steroids are hormones
that are important regulators
of animal development
and metabolism at very
low concentrations.
A well known steroid,
cholesterol, is present
in membranes of animal
tissues. Other steroids
include testosterone
(a male sex hormone),
cortisone (an adrenocortical
hormone), estrone (a
female sex hormone),
and progesterone.
Strain
A population of cells
all descended from a
single cell.
Strength
The concentration of
the drug substance (for
example, weight/weight,
weight/volume, or unit
dose/volume basis),
and/or the potency,
that is, the therapeutic
activity of the drug
product as indicated
by appropriate laboratory
tests or by adequately
developed and controlled
clinical data (expressed,
for example, in terms
of units by reference
to a standard).
STS
Sublimation
The process of vaporizing
a solid substance by
heat and then condensing
it (without its having
passed through a liquid
state in either direction),
a process of purification
by separating the nonvaporizable
impurities, a process
analogous to the distillation
of liquids.
Submerged Arc Welding
(SAW)
An arc welding process
that produces coalescence
of metals by heating
them with an arc or
arcs between a bare
metal electrode or electrodes
and the work. A blanket
of granular, fusible
material on the work
shields the arc. Pressure
is not used and filler
metal is obtained from
the electrode and sometimes
from a supplemental
source (welding rod,
flux, or metal granules).
Substrate
Reactive material -
the substance on which
an enzyme acts.
Subsurface Carbon Enrichment
In metals, a rise in
the carbon signal at
depths from 15 to 20
angstroms (Å). This
indicates that organic
material is buried in
cracks, crevices, pits,
or smeared material.
Subsurface carbon is
most commonly found
in materials having
rough morphology generally
associated with machining
processes.
Supernatant
The material floating
on the surface of a
liquid mixture (often
the liquid component
that has the lowest
density).
Surface Finishes
This term shall apply
to all interior surface
finishes accessible
and inaccessible, that
directly or indirectly
come in contact with
the designated product
in bioprocessing equipment
and distribution system
components (ASME BPEa-2000).
Final criteria shall
be determined by Ra
values rather than polishing
methods.
For Piping, Tubing,
and Fittings:
1. As fabricated
2. Pickled and/or passivated
3. Bright hydrogen annealed
4. Mechanically polished
5. Mechanically buffed
6. Chemically polished
7. Electropolished
For Sheet, Strip, and
Plate:
1. As fabricated. Without
any specific surface
treatments.
2. Rolled Finish. Manufactured
by either hot or cold
rolled process.
3. No. 1. A dull, hot
rolled finish, annealed
and pickled.
4. No. 2D. A dull, cold
rolled finish, annealed
and pickled.
5. No. 2B. A bright,
cold rolled finish,
annealed and pickled.
6. No. 4. A general
purpose polished finish
widely used for architectural
panels, trim, and sanitary
equipment. Following
initial grinding with
coarse abrasives, the
surface is finally finished
with lubricated 150
grit abrasive belts.
7. No. 4S. Processed
as No. 4 except the
final surface is polished
to a smother finish.
The purchaser must specify
this alternative finish;
the specification must
state a No. 4 finish,
using a 240 or 320 grit
mechanical polish, whose
particular surface roughness
must meet the specified
Ra value.
8. No. 6. A dull finish
having a lower reflectivity
than No. 4. It is produced
by a tampico brushing
in a medium of abrasive
and oil and is used
primarily for architectural
applications.
9. No. 7. A finish with
a high degree of reflectivity,
produced by buffing
to a finely ground surface
without removing the
grit lines.
10. No. 8. The most
reflective finish, obtained
by polishing with successively
finer abrasives and
buffing extensively
with very fine buffing
rouges. This finish
is most widely used
for press plates, mirrors,
etc.
For Wrought and Cast
Forgings:
1. As fabricated or
machined
2. Mechanically ground,
polished, or buffed
3. Abrasive blast cleaned,
using one of the following
methods:
a. Sand blast
b. Shot blast
c. Glass blast
d. Wet blast
4. Slurry polished
5. Roll deburred
6. Chemically cleaned
a. Acid washed (pickled
and passivated)
b. Solvent washed
7. Electropolished
Surface Iron Oxide
Layer
Surface iron oxide layer
present when the 316L
stainless steel's iron
composition signal is
higher than its chromium
signal at the surface.
Surface Residual
A foreign substance
that adheres to a surface
by chemical reaction,
adhesion, adsorption,
or ionic bonding (for
example, corrosion,
rouging, and staining).
Surface Texture
The repetitive or random
deviations of the nominal
metal surface from the
three-dimensional topography
of the surface. Surface
texture includes roughness,
waviness, lay, and flaws.
Surface Water
Any water where the
source is above ground
such as rivers, lakes,
and reservoirs. Surface
waters are usually higher
in suspended matter
and organic material
and lower in dissolved
minerals than well water.
Surfactant
Any substance that changes
the nature of a surface,
such as lowering the
surface tension of water.
Suspended Solids
Undissolved solids that
can be removed by filtration.
Determined by a filter
paper before and after
filtration of a water
sample.
Suspension
A specific category
of pharmaceutical product
that must be in a colloidal
dispersion (suspension)
for proper action. For
example, Kaolin/Pectin
works as an adsorbant
because its high surface
area in suspension.
Symbiosis
The phenomenon of two
entities performing
a joint function that
neither entity can perform
alone.
Synthesis
Creating products through
chemical and enzymatic
reactions.
System Specifications
Descriptions of how
the system will meet
the functional requirements.
T
Tangential Flow Filtration
A separation method
that transfers components
of one system (stream)
into another. The stream
the product is being
extracted from crosses
the stream that the
product is being transferred
to, multiple times.
Taxonomy
The development of approaches
to organize and summarize
our knowledge about
the variety or organisms
that exist.
Tay-Sachs Disease
An inherited disease
of infancy characterized
by profound mental retardation
and early death; it
is caused by a recessive
gene mutation.
Team Biologics
A partnership between
FDA's Office of Regulatory
Affairs (ORA) and CBER
to focus on inspectional
and compliance issues
in biologics. Its goal
is to ensure the quality
and safety of biologic
products and resolve
inconsistencies.
T-Cell (T-lymphocyte)
A blood cell, probably
originating from bone
marrow, but which matures
in the thymus. Some
T-cells are responsible
for cell-mediated immunity
and in the production
of antibodies.
Telomere The end of
a chromosome. This specialized
structure is involved
in the replication and
stability of linear
DNA molecules.
Temperature
A specific degree of
heat intensity. There
are three temperature
designations associated
with psychrometrics:
1. Dry Bulb (DB) - The
air temperature as measured
by a standard thermometer.
2. Wet Bulb (WB) - The
air temperature measured
by a thermometer with
its reservoir bulb wrapped
in a moistened cloth
wick and exposed to
an air stream moving
at a velocity of 1,000
feet per minute. 3.
Dewpoint temperature
(DP) - Also called Saturation
Temperature is the temperature
at which condensation
of moisture begins (air
is holding 100% of the
moisture it can) when
the air is cooled, measured
in °F.
Terminal Sterilization
The process applied
to product sealed in
its final container
that transforms a non-sterile
product into a sterile
one.
Terminal Sterilization
This term is a gross
misnomer because it
refers specifically
to the terminal heat
sterilization of LVPs
usually by steam.
Terminally Ill
For an individual, it
means that the subject
has a life expectancy
of six months or less
as stated in writing
by his or her attending
physician and surgeon.
Test Procedure
A sequence of activities
which when executed
successfully provides
documentary evidence
that part of the system
works as specified.
Theoretical Yield
The quantity that would
be produced at any appropriate
phase of manufacture,
processing, or packing
of a particular drug
product, based upon
the quantity of components
to be used, in the absence
of any loss or error
in actual production.
Thermophile
An organism that grows
best at greater than
50ºC (122ºF).
Thermophilic (Of A
Microorganism)
With optimum temperature
for growth above 45ºC,
many thermophilic bacteria
exist at high temperatures
(greater than 80ºC)
and many of their enzymes
which posses high thermal
stability, are of great
commercial interest.
Thrombin (Blood Coagulation
Factor II)
An enzyme (the activated
thrombogen) formed in
the blood, after this
is shed, that converts
fibrinogen into fibrin
for clot formation.
It is formed from conjunction
of prothrombin and calcium
salts. It is also a
sterile protein substance
prepared from prothrombin
of bovine origin through
interaction with thromboplastin
in the presence of calcium.
Bovine thrombin is often
used to aid production
of serum from "salvage"
plasma.
Thrombosis
Clotting within a blood
vessel that may cause
infarction of tissues
supplied by the vessel.
Throughput Volume
The amount of solution
passed through an exchange
bed before the resin
is exhausted.
A pyrimidine component
of nucleic acid first
isolated from the thymus.
TIG (Tungsten Inert
Gas)
Time Stamp
A part of the audit
trail that clearly documents
the sequence of events
in human terms, helping
to authenticate an electronic
signature and minimizing
the chances of signer
repudiation. A local
time stamp correlates
with the whereabouts
of the signer. With
client-server data systems
used by international
companies and records
accessed from remote
sites (such as on business
trips), time stamps
that reflect the local
time of only the user
might make the sequence
of actions for an individual
record appear inconsistent.
For example, the approval
by a peer reviewer could
be signed at 9:00 a.m.
on a chromatographic
analysis that was performed
at 11:00 a.m. in a different
time zone. Local time
stamps should probably
be supplemented consistently
with the time stamp
of a remote server,
with one stamp clearly
labeled as local.
Tincture of Iodine
A germicidal solution
of iodine in aqueous
alcohol used primarily
as antiseptic on skin
and tissue.
Tissue Culture
Growing mammalian cells
in the laboratory in
a tissue culture medium
(in vitro). For example,
this allows researchers
to determine the effects
of various chemicals
on mammalian cells without
experimenting directly
on live animals or man.
Since a molecule of
some toxic substances
can harm a single mammalian
cell, even one part-per-billion
of some impurities can
affect a tissue culture.
Therefore, water used
to make up tissue culture
media should be extremely
pure.
Titer
A measured sample -
the strength of a solution
or the concentration
of a substance (as an
antibody) in solution
as determined by titration.
Titration
Volumetric analysis
by means of the addition
of definite amounts
of a test solution to
a solution of a known
amount of the substance
analyzed.
TNT (Tumor Necrosis
Therapy)
Therapeutic agents that
target dead and dying
cells found primarily
at the core of the tumor.
Toe of Weld
The junction between
the face of a weld and
the base material.
Tolerance
Failure to mount an
immune reaction on exposure
to what would normally
be an antigenic substance.
Ton of Refrigeration
A unit used to indicate
the size of a refrigeration
unit. One ton of refrigeration
effect is equivalent
to removing 12,000 Btu/hr
of heat, or melting
one ton of ice in a
24-hour period.
Topical
A medication applied
to the skin, an ointment.
Usually a medicament
suspended in a carrier
such as petrolatum or
another oil based carrier.
Filtration at elevated
temperatures is usually
possible.
Topical Product
A pharmaceutical product
meant to be applied
to the skin or soft
tissue in the form of
liquid, cream, or ointment,
and therefore needs
not be aseptic. Sterile
ophthalmic products
throughout are manufactured
aseptically.
Total Bacteria Count
An estimation of the
total number of bacteria
in a sample based usually
on Standard Methods
procedures for collecting,
incubating, and counting
colony-forming units
(cfu).
Total Dissolved Solids
(TDS) The term used
to describe inorganic
ions in the water. Usually
measured by electrical
conductance of the water
corrected to 25°C, and
expressed as ppm (parts
per million).
Total Heat (TH)
The sum of sensible
heat and latent heat.
Total Ionized Solids
Concentration of dissolved
ions in solution expressed
in concentration units
of Sodium Chloride (NaCl).
It determines the operating
life of ion exchange
resins and is calculated
from measurements of
Specific Resistance.
Total Organic Carbon
(TOC)
A measure of the level
of organic impurities
in water by their carbon
content that determines
the operating life of
activated carbon beds.
This is one of the parameters
used to determine the
purity of Semiconductor
Grade water. Feed water
will have TOC measured
in ppm (parts per million),
and ultrapure water
(UPW) will have TOC
measured in ppb (parts
per billion).
Total Solids
Total solids in water
include both dissolved
and suspended solids.
Determined by weighing
sample before and after
evaporation.
Toxic
Pertaining to a substance
that is harmful.
Toxicology
A science that deals
with poisons, their
effects, and the problems
involved.
Toxin
A substance produced
by microorganisms that
can inhibit cell growth
in tissue culture and
may cause temperature
rise in animals.
Toxin
Any poisonous agent,
especially a poisonous
substance produced by
one living organism
that is poisonous to
other organisms. Toxins
are usually very unstable,
notably toxic when introduced
into the tissues, and
typically capable of
inducing antibody formation.
Toxoid
An antigenic toxin.
Example is tetanus toxoid
that is a bacterial
vaccine.
TPA (Tissue Plasminogen
Activator)
A recombinant drug used
in the management of
heart attacks to prevent
clotting. Produced by
Genentech and one of
the first successful
recombinant DNA drugs
to be commercialized.
Trace Analysis
Analyzing constituents
present in ppm and ppb
concentrations. Trace
analysis requires extremely
pure reagents, made
with ultrapure Type
I reagent grade water.
Traceability
A prerequisite for trustworthy
records, apart from
data security. Traceability
is the part of the laboratory
data system audit trail
that holds the evidence
of who did what to a
record and when.
Tracer
A radioactively labeled
nucleic acid component
included in a reassociation
reaction in amounts
too small to influence
the progress of reaction.
Transcription
The process by which
the genetic information
encoded in the gene,
represented as a linear
sequence of deoxyribonucleotides
(DNA), is copied into
an exactly complementary
sequence of ribonucleotides
known as mRNA (messenger
RNA).
Transduction
The transfer of genetic
material from one cell
to another by means
of a viral vector (for
bacteria, the vector
is Bacteriophage).
Transfection
The acquisition of new
genetic markers by addition
of viral DNA to cells.
Transfer Panel
A panel to which process
and utilities are piped,
allowing cross connections
between different use
points. A jumper spool
is used to connect the
desired process/utility
users and mechanically
preclude erroneous connections
to other lines.
Transfer RNA (tRNA)
A class of RNA having
structures with triplet
nucleotide sequences
that are complementary
to the triplet nucleotide
coding sequences of
mRNA. The role of tRNAs
in protein synthesis
is to bond with amino
acids and transfer them
to the ribosomes, where
proteins are assembled
according to the genetic
code carried by mRNA.
Transfer Systems
Equipment allowing the
introduction and removal
of material, toxic and/or
sterile, with continuous
protection to both operator
and product.
Transformation
A process by which the
genetic material carried
by an individual cell
is altered by incorporation
of exogenous DNA into
its genome.
Transgenics
The alteration of a
plant or animal's DNA
such that it contains
a gene from another
organism. There are
two types of cells in
animal and plants, germ
line cells (the sperm
and egg in animals,
pollen and ovule in
plants) and somatic
cells (all other cells).
Transgenic animals have
alterations in their
germ line DNA so the
alterations are passed
on to the offspring.
That is done to produce
therapeutics, to study
disease, and to improve
farm animals. Transgenic
plants have been created
for increased resistance
to disease and insects
as well as to make biopharmaceuticals.
Translation
The process in which
the genetic code carried
by mRNA directs the
synthesis of proteins
from amino acids.
Treatment Investigational
New Drug
An Investigational New
Drug that makes a promising
new drug available to
desperately ill patients
as early in the drug
development process
as available. FDA permits
the drug to be used
if there is preliminary
evidence of efficacy
and it treats a serious
or life-threatening
disease, or if there
is not comparable therapy
available.
Trihalomethanes
Compounds present in
the feed water that
are formed by the reaction
of Chlorine and the
organic material in
the water. Activated
carbon and degasification
can reduce THMs.
Tube Size
Tube is sized by its
nominal outside diameter.
For bioprocessing equipment,
tube does not include
pipe.
Tumor
An abnormal growth of
cells. Also defined
as a circumscribed growth,
not inflammatory in
character, arising from
preexisting tissue,
but independent of the
normal rate or laws
of growth of such tissue,
and subserving no physiological
function.
Tumor Pathogenesis
Morphological and physiological
changes associated with
tumor growth.
Tumor-Suppressor Genes
Genes that normally
restrain cell growth
but, when missing or
inactivated by mutation,
allow cells to grow
uncontrolled.
Turbidity
A suspension of fine
particles that obscures
light rays but requires
many days for sedimentation
because of small particle
size.
Turnover
Also known as "hand
over" in the U.K.
It is a formal transfer
of custody for a system
or unit to another group,
department, or operating
company.
Turnover Package (TOP)
A collection of pertinent
design, construction,
vendor, and operational
documentation. This
collection of documentation
is used for the qualification
and process validation
activity, as well as
reference and single
source information for
the life of any particular
system, process, or
piece of equipment.
Two-Bed Deionizer
Separate beds or layers
of cation and anion
exchange resins. Results
in lower purity than
mixed-bed deionization,
but provides higher
capacity in terms of
throughput.
Tyrosine (Tyr)
A Phenolic alpha amino
acid; a precursor of
the hormones epinephrine,
norepinephrine, thyroxine,
and triiodothyronine,
and of the black pigment
melanin.
U
Ultra Low Penetration
Air filters (ULPA)
Extended media dry filters
in a rigid frame that
have a minimum particle-collection
efficiency of 99.999%
for particles greater
than or equal to 0.12µm
in size. Most commonly
used in microelectronics,
few uses in pharmaceuticals.
Ultracentrifugation
The separation of macromolecules
on the basis of their
density and shape using
the gravitational field
generated in a high-speed
centrifuge. It is used
in rDNA work for the
separation of RNA and
DNA, and for purification
of plasmids.
Ultrafiltration
Molecular sieves; membranes
with pores small enough
to remove large molecules.
Rated in terms of nominal
molecular weight cutoff.
A 10,000 Dalton (molecular
weight) UF membrane,
for example, will remove
bacterial pyrogens that
are typically in the
range of 20,000 Daltons.
Ultrafine Particle
Particle with an equivalent
diameter less than 0,1µm.
ISO 14644-1
Ultrapure Water
Water with a specific
resistance higher than
1 megohm-cm. In the
laboratory, it usually
refers to Type I reagent
grade water. Anything
in laboratory water
that is not H2O is an
impurity. Although chemically
pure water is not attainable,
ultrapure water systems
are now capable of reducing
impurities down to the
limits of detection.
Ultraviolet Oxidation
Ultraviolet radiation
is employed in water
purification for the
photochemical oxidation
of organic impurities
resulting in HPLC grade
water with organic impurity
levels below 0.0005
absorbance units.
Ultraviolet Radiation
Light in the wavelength
region 200-300 nm, used
to detect RNA or DNA
that has the fluorescent
dye, ethidium bromide,
bound to it.
Ultraviolet Sterilizer
Ultraviolet lamps used
to kill microorganisms
in water.
Ultraviolet TOC Reduction
An ultraviolet source,
which partially oxidizes
organic compounds to
ionic species that can
be removed. It relies
on 185 nm (nanometer)
radiation from "ozone
producing" mercury
lamps (along with 254nm
germicidal radiation).
Generally has a longer
contact time than sterilization
alone.
Unicellular
Composed of only a single
cell.
Unidirectional Airflow
Previously referred
as "laminar"
airflow, is the "rectified
airflow through the
entire cross section
of a clean zone with
a steady velocity and
approximately parallel
streamlines. This type
of airflow results in
a directed transport
of particles from the
clean zone". ISO
14644-4.
Uniform Building Code
(UBC)
The most widely adopted
model building code
in the United States
is a performance based
document meeting the
needs of government
units charged with the
enforcement of building
regulations.
Uniform Fire Code™
The premier model fire
code in the United States
sets forth provisions
necessary for fire prevention
and fire protection.
Published by the International
Fire Code Institute
(IFCI) and endorsed
by the Western Fire
Chiefs Association,
the International Association
of Fire Chiefs, and
the International Conference
of Building Officials
(ICBO), it contains
code provisions compatible
with the Uniform Building
Code, and standards
referenced from the
code provisions.
Uniform Mechanical
Code™
A document that provides
a complete set of requirements
for the design, construction,
installation, and maintenance
of heating, ventilating,
cooling and refrigeration
systems; incinerators
and other heat-producing
appliances.
Uniform Zoning Code™
A code dedicated to
intelligent community
development and to the
benefit of the public
welfare by providing
a means of promoting
uniformity in zoning
laws and enforcement.
Unit Dose Defines an
SVP that must be administered
in one dose. Unused
contents must be discarded.
United States Pharmacopeia
(U.S.P.)
Universal Precautions
Precautions taken when
handling, storing, transporting,
or shipping items or
specimens containing,
or contaminated with
human blood and body
fluids: all such materials
are treated as infectious.
Unsaturated Fatty Acid
A fatty acid containing
one or more double bonds.
Unstable (Reactive)
Material
A material other than
an explosive, which
in the pure state or
as commercially produced
will vigorously polymerize,
decompose, condense
or become self-reactive
and undergo other violent
chemical changes, including
explosion, when exposed
to heat, friction or
shock, or in the absence
of an inhibitor or in
the presence of contaminants
or in contact with noncompatible
materials. Unstable,
reactive materials are
subdivided as follows:
1. Class 4 - Materials
that in themselves are
readily capable of detonation
or of explosive decomposition
or explosive reaction
at normal temperatures
and pressures. This
class includes materials
that are sensitive to
mechanical or localized
thermal shock at normal
temperatures and pressures.
2. Class 3 - Materials
that in themselves,
are capable of detonation
or of explosive decomposition
or explosive reaction
but which require a
strong initiating source
or which must be heated
under confinement before
initiation. This class
includes materials that
are sensitive to thermal
or mechanical shock
at elevated temperatures
and pressures.
3. Class 2 - Materials
that in themselves are
normally unstable and
readily undergo violent
chemical change but
do not detonate. This
class includes materials
which can undergo chemical
change with rapid release
of energy at normal
temperatures and pressures
and which can undergo
violent chemical change
at elevated temperatures
and pressures.
4. Class 1 - Materials
that in themselves are
normally stable but
which can become unstable
at elevated temperatures
and pressures.
Upward Compatibility
Refers to software that
runs not only on the
computer for which it
was designed, but also
on newer and more powerful
models. In the context
of CFR 21 Part 11, compatibility
plays an important role
in ensuring that legacy
data can be moved (copied)
accurately and completely
to a new system. Without
it, legacy systems would
have to be maintained
as long as the records
contained in them are
kept. (also see:
Uracil
A pyrimidine base important
as a component of ribonucleic
acid (RNA). Uracil is
capable of forming a
base pair with adenine.
User Interface
Dials, knobs, operating
system commands, graphical
display formats, and
other devices provided
by a computer or a program
to allow users to communicate
and use the computer
or program. A Graphical
User Interface (GUI)
provides its user with
a "picture oriented"
way to interact with
technology.
U.S.P. (United States
Pharmacopeia)
A compendium of testing
and purity criteria
for pharmaceuticals,
ancillaries, and raw
materials. (also see:
National Formulary (NF))
Utility Systems
Facility wide systems
not tailored to a specific
process and that do
not have contact with
the drug substance or
potential drug substance.
V
Vacuoles
Membrane-bound organelles
of low density responsible
for food digestion,
osmotic regulation,
and waste product storage.
Vacuoles may occupy
a large fraction of
cell volume (up to 90%
in plant cells).
Vaccine
A preparation of microbial
antigens that provokes
an immune response (i.e.
the production of antibodies)
on injection, thus conferring
immunity on the recipient.
There are three types
of vaccines:
1. Those containing
material from a nonvirulent
organism that retains
its immunogenicity but
does not result in infection.
2. Those containing
a modified toxin (a
toxoid) that has lost
its toxic properties
but retain its immunogenicity.
3. Those containing
live, attenuated organisms
(i.e. genetic variants
of a virus or bacterium)
that are antigenically
similar to the original
strain but lack virulence.
Recombinant DNA research
has allowed the production
of new and more specific
vaccines. For example,
the gene for the B antigen
of hepatitis virus has
been cloned in E. coli,
the protein expressed
and a specific anti-B
antiserum produced which
can be used as a vaccine.
Vaccine
A preparation of killed
microorganisms, living
attenuated organisms,
or living fully virulent
organisms that is administered
to produce or artificially
increase immunity to
a particular disease.
Vacuum Degasification
The process of removing
dissolved and entrained
gases from the Reverse
Osmosis (RO) product
water by creating a
vacuum in a tower through
which this water flows.
The degasifier may be
located before the RO
system but the majority
of the time will be
located after. The most
prevalent gas present
is Carbon Dioxide (CO2),
which may have been
generated during pH
adjustment of the RO
feed water. The anion
exchange resin can remove
CO2 but using the vacuum
degasifier can reduce
that load. The other
gas of concern is Oxygen,
which can also be removed
by a vacuum degasifier.
Validation
A documented program
that provides a high
degree of assurance
that a specific process,
method, or system will
consistently produce
a result meeting pre-determined
acceptance criteria.
Validation Master Plan
The documented plan
for qualification of
a facility or part of
a facility that identifies
the layout of the operation,
the associated utilities
and systems, the equipment,
and the processes to
be validated. The validation
master plan also provides
preliminary information
as to the extent of
the qualification and
validation (IQ, OQ,
PQ), required documentation,
SOPs, acceptance criteria
and responsibilities.
Validation Master Plans
should also establish
the cross reference
of qualification projects
by product, system,
discipline, etc.
Validation Protocol
A written plan describing
the process to be validated,
including production
equipment and how validation
will be conducted. Such
a plan would address
objective test parameters,
product and process
characteristics, predetermined
specifications, and
factors, which will
determine acceptable
results.
Validation Protocol
(from ICH API)
A written plan stating
how validation will
be conducted and defining
acceptance criteria.
For example, the protocol
for a manufacturing
process identifies processing
equipment, critical
process parameters/operating
ranges, product characteristics,
sampling, and test data
to be collected, number
of validation runs,
and acceptable test
results.
Vapor Pressure
Dalton's Law for a mixture
of perfect gases states
that the mixture pressure
is equal to the sum
of the partial pressures
of the constituents.
The partial pressure
of moisture is called
vapor pressure, and
is expressed as: Total
Pressure (Pt) = Partial
Pressure of Air (Pa)
+ Partial Pressure of
Moisture (Pv)
Vascular Targeting
Agents (VTAs)
Multifunctional agents
that are home to the
capillaries and vessels
of solid tumors.
Vector
An agent, such as an
insect, that can carry
a disease-producing
organism from one host
to another; the agent
used to carry new genes
into cells. Plasmids
currently are the vectors
of choice, though viruses
and other bacteria may
sometimes be used. These
molecules become part
of the cell protoplasm.
VEAs (Vasopermeation
Enhancement Agents)
A new generation of
drugs that increase
the uptake of therapeutic
agents to solid tumors.
Vegetative Form In bacteria,
a stage of active growth,
as opposed to a resting
state or spore formation.
Vehicle
Any solvent or carrier
fluid in a pharmaceutical
product that has no
pharmacological role.
For example, water is
the vehicle for xilocaine
and propylene glycol
is the vehicle for many
antibiotics.
Verification
The act of reviewing,
inspecting, testing,
checking, auditing,
or otherwise establishing
and documenting whether
items, processes, services,
or documents conform
to specified requirements.
(also see: IQ (Installation
Qualification))
Veterinary
Referring to pharmaceuticals
or biologicals intended
for animal use. Historically
veterinary products
were made by less than
"Good Manufacturing
Products". Today,
however, the GMP's refer
to both human and veterinary
products.
Viable Living
Viable Organism Capable
of living and reproducing.
Thus, nothing is sterile
as long as it contains
even a single viable
organism.
Vial
A final container for
a parenteral or diagnostic
product. Sealed with
a rubber closure and
over-seal. Generally
required to be class
I borosilicate glass.
Viral Antigens
Specific proteins on
the capsid of a virus
that can act as inducers
of antibody formation.
Virion
A fully formed, mature
virus. Infection is
initiated in a cell
by a virion.
Virucide
An agent that destroys
or inactivates viruses.
Virulence
The disease-producing
power of a microorganism.
Virus
A simple, noncellular
parasite that can reproduce
only inside living cells.
The simple structure
of viruses is their
most important characteristic.
Most of them consist
only of a genetic material
- either DNA or RNA
- and a protein coating.
Some also have membranous
envelopes. Viruses are
"alive" in
that they can reproduce
themselves - although
only by taking over
a cell's synthetic machinery
- but they have none
of the other characteristics
of living organisms.
Viruses cause a large
variety of significant
diseases in plants and
animals, including humans.
Viscosity
The tendency of a fluid
to resist flowing because
of molecular attraction
(cohesion).
Vitamin
Term coined in 1911
(vita, Latin word for
life, and the chemical
term amine) by polish
biochemist, Casimir
Funk, represents one
of a group of organic
substances, some of
which are of unknown
composition, present
in minute amount in
natural foodstuffs which
are essential to normal
metabolism. A lack of
which in the dietary
causes deficiency diseases.
Vitamins are commonly
classified into two
groups, the fat-soluble,
and the water-soluble.
Vitamins A, D, E, and
K are fat-soluble. Vitamin
C and members of the
vitamin B complex group
are water-soluble. In
general, the vitamins
play catalytic and regulatory
roles in the body's
metabolism. Among the
water-soluble vitamins,
the B vitamins apparently
function as coenzymes.
Vitamin's C coenzyme
role, if any, has not
been established. Part
of the importance of
vitamin C to the body
may result from its
strong antioxidant action.
The actions of the fat-soluble
vitamins are less well
understood. Some of
them, too, may contribute
to enzyme activity,
and some of them are
essential to the functioning
of cellular membranes.
VPHP
Microbiodecontamination
Technology used to decontaminate
the exposed, internal
surfaces within a sealed
isolator and the exposed,
external surfaces of
materials and components
placed within the sealed
isolator. It consists
of four distinctive
phases: 1. Dehumidification
- Lowers humidity and
increases temperature
2. Conditioning - "Ramp-up"
(VPHP) at or below saturation
conditions 3. Sterilization
- Steady-State (VPHP)
at or below saturation
conditions 4. Aeration
- Reduces the VPHP to
Safe Levels.
VTAs
W
WAN(Wide Area Network)
Network with computers
far apart, connected
by telephone lines or
radio waves.LAN (Local
Area Network))
Warning Letter
The most serious FDA
postaudit (after inspection)
letter notifying a manufacturer
of adverse finding and
giving it 15 days to
reply.
Water Hammer
A tremendous force produced
by rapid interruption
of linear flow of a
non-compressible fluid.
Most commonly occurs
when fast acting valves
are closed in a high
flow liquid system.
Water Treatment
Water treatment, also
referred to as water
conditioning, can consist
of adding or removing
chemicals to change
the properties of water.
In water softening,
for example, sodium
ions are substituted
for metallic ions that
cause "hardness"
thus reducing the scale-forming
tendencies of water.
Water purification on
the other hand, always
consists of removing
undesirable impurities.
Waviness
The more widely spaced
component of surface
texture. Unless otherwise
noted, waviness includes
all irregularities whose
spacing is greater than
the roughness sampling
length. Waviness may
result from such factors
as machine or work deflection,
vibration, chatter,
heat treatment or warping
strains. Roughness may
be considered as superimposed
on a "wavy"
surface.
Western Blot
A procedure in which
a mixture of proteins
is separated on a polyacrylamide
gel and then transferred
to a nylon membrane.
The membrane may then
be treated with reagents
such as specific antibodies
to locate a protein
of interest.
Wetted Surface
The surface(s) of any
valve or component that
will be exposed to a
fluid (liquid or gas)
when in service.
WFI (Water For injection),
U.S.P.
WFI is water purified
by distillation or by
reverse osmosis, it
contains no added substance.
WFI meets the purity
requirements under Purified
Water. Although not
intended to be sterile,
it meets a test for
a limit of bacterial
endotoxin. It must be
produced, stored, and
distributed under Sterile
Water for Injection.
White Blood Cell
A blood cell containing
no respiratory pigment.
In vertebrates it may
be a polymorphonuclear
leukocyte, a lymphocyte
or a monocyte.
Workstation
An open or enclosed
work surface, usually
with direct air supply.
Worst Case
The highest or lowest
value of a given control
parameter actually evaluated
in a validation exercise.
X
X Chromosome
A sex chromosome that
usually occurs paired
in each female cell
and single in each male
cell in species in which
the male typically has
two unlike cell chromosomes.
Xenobiotics
Industrial chemicals
that have a chemical
structure not found
in natural compounds
that may resist degradation
by microorganisms.
XPS(X-Ray Photoelectron
Spectroscopy) or ESCA
(Electron Spectroscopy
for Chemical Analysis)
A surface-sensitive
technique capable of
detecting all elements
with an atomic number
greater than that of
helium. ESCA provides
data on the outermost
several atomic layers
of a material, and has
a sensitivity in the
order of 0.5 atomic
percent. A primary advantage
of ESCA is that it can
both determine and quantify
the chemical state of
the elements detected
(i.e. metallic state
or oxide state).
Y
Y Chromosome
A sex chromosome that
is characteristic of
male zygotes in species
in which the male typically
has two unlike sex chromosomes.
Yeast Artificial Chromosome
A vector used to clone
DNA fragments (up to
400 kb); it is constructed
from the telomeric,
centromeric, and replication
origin sequences needed
for replication in yeast
cells.
Yeasts
Unicellular fungi belonging
mainly to the Ascomycetes
that usually multiply
by budding. Their commercial
significance lies in
their ability to secrete
enzymes. For example,
in the brewing and baking
industries, it is a
source of vitamins and
proteins. They can also
be used as excipients
in rDNA technology.
Yield, Expected
The quantity of material
or the percentage of
theoretical yield anticipated
at any appropriate phase
of production based
on previous laboratory,
pilot scale, or manufacturing
data.
Yield, Theoretical
The quantity that would
be produced at any appropriate
phase of manufacture,
processing, or packing
of a particular API
(Active Pharmaceutical
Ingredient) or intermediate,
based upon the quantity
of components to be
used, in the absence
of any loss or error
in actual production.
Z
Zeolite
Naturally occurring
or synthetic permutite,
a hydrated alkali-aluminum
silicate that exhibits
limited base exchange.
Used as an ion exchange
medium for the softening
of hard water.
Zeta Potential
The charge or potential
existing at the surface
of a particle. It is
the positive charge
measured at the surface
of the membrane across
the pH range.
Zoonosis
Any disease in humans
acquired from one of
the lower animals, rabies
is an example.
Zygote
Single cell formed from
the conjugation of gametes
(egg and sperm cells).
The zygote has twice
as many chromosomes
as do gametes.
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