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[ BIOTERMINOLOGY ]

A Guide to the
Biopharmaceutical
Lexicon
2012 edition
[ BIOTERMINOLOGY ]

BIOTERMINOLOGY AND
DEFINITIONS
A
absorption Removal of a particular
tance of the results of analytical procedures
which the drug substance or drug product or
materials at other stages of their manufac-
molecule from a sample by accumulation ture should meet. [From ICH Q6B]
into a bound water volume such as might ACN Acetonitrile; the most frequently
be present in a densely fibrous material. In used solvent in HPLC, commonly used as
pharmacology (and more specifically phar- an eluent.
macokinetics), absorption is the movement acidic variant A product variant that
of a drug into the bloodstream. Absorption exhibits a more negative charge character
involves several phases. First, the drug needs by IEX or CE than the primary biotherapeu-
to be introduced via a route of administra- tic form.
tion (oral, via the skin, etc.) and in a specific active starting material The raw materi-
dosage form such as a tablet, capsule, and so al that is identified as directly related to the
on. (See adsorption). active chemical comprising the product, and
accelerated stability tests Studies in is defined at the first stage during chemical
which the product is stored under stress con- synthesis at which part or most of the critical
ditions (for example, 45 C and high humidity moieties are present. Defining active starting
over three to six months) and observed for material defines the step at which compli-
signs of degradation; used to predict long- ance with cGMP requirements begins during
term storage patterns. manufacturing. For biopharmaceuticals, this
acceptance criteria Numerical limits, term is not used.
ranges, or other suitable measures for accep- acute Describes a disorder as a one-time
Following acronyms that appear in brackets throughout the guide represent the sources of definitions:
FDA QSG definition is the one that appears in the US FDAs Quality Systems guidance.
ICH Q6B definition is the one that appears in the International Conference on Harmonization (ICH) Q6B guideline,
Test Procedures and Acceptance Criteria for Biotechnological/Biological Products.
ICH Q8 definition is the one that appears in the ICH Q8 guideline, Pharmaceutical Development.
ICH Q9 definition is the one that appears in the ICH Q9 guideline, Quality Risk Management.
ICH Q11 under review; definition is the one that appears in the ICH Q11 guideline, Development and Manufacture of
Drug Substances (chemical entities and biotechnical/biological entities).
ISO 14971 Refers to the International Organization for Standardizations standard 14971,
Medical DevicesApplication of risk management to medical devices.
ISO/IEC Guide 51 Refers to the the joint ISO and IEC (International Electrotechnical Commission) publication,
Safety aspectsGuidelines for their inclusion in standards.
ISO Guide 73 Refers to ISO Guide 73, Risk managementVocabularyGuidelines for their use in standards.

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[ BIOTERMINOLOGY ]

condition (an injury or infection), rather than


as a chronic disease such as diabetes.
ADME Absorption, distribution, metabo-
lism, and excretion.
adjuvant A chemical agent added to
vaccines to boost the immune response to
the vaccine antigen.
ADR Adverse drug reaction, an undesir-
able effect that may be caused by a study
drug (see also adverse events). One of the most frequently used sol-
adsorption Adherence of molecules in vents in chromatographic analysis is
ACN, acetonitrile.
solution or suspension to cells or other
moleculesor to solid surfaces, such chromatography uses chelation.
as chromatography media. Compare to affinity tag (or tail) An amino acid
absorption. sequence added to a protein to facilitate
adventitious agents Acquired, ac- purification by affinity chromatography.
cidental contaminants in a cell line, such as agarose A polysaccharide (sugar)
viruses and toxins; often infectious agents. obtained from seaweed and used as a solidi-
adverse events (see also ADR) Unde- fying agent (agar) in microbial culture; also
sired effects or toxicity in a patient due to used in gel electrophoresis.
exposure (often to a drug or medical device, aggregate A clustered mass, as of
but not limited to those). Adverse events protein molecules; or to cluster together in
must be notified to the sponsor, who is such a way. Aggregates of cells (solid, fluffy,
required to perform a written investigation or pelletized) can clog the pores of filters or
into the root causes, and may need to take other fermentation apparatus.
other corrective or preventive actions. (See Ala Alanine; one of more than 20 natu-
complaints, CAPA) rally occurring amino acids.
aerobic Growing in the presence of albumins Protein constituents of blood
oxygen. A strict aerobe grows only under plasma and serum also found in muscle, egg
such a condition. white, and milk.
affinity Attraction between particles or alkylation The introduction, by substitu-
substances; relatively speaking, a measure tion or addition, of an alkyl group into an
of the attraction of one molecule toward organic compound; alkylating agents are
another. various substances that contain an alkyl
affinity chromatography A chro- radical and that can, therefore, replace a
matographic method that makes use of the hydrogen atom in an organic compound;
specific binding of one molecule to another; alkylation is used to prevent refolding of
immunoaffinity chromatography uses an- already reduced proteins during peptide
tibodies, for example, and metal affinity mapping.

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alpha helix (-helix) A coil or spiral anaerobic Growing in the absence of air
element of protein secondary structure. or oxygen. Some anaerobic organisms are
amino acid analysis Hydrolysis of a killed by brief exposure to oxygen, whereas
protein or peptide into its individual residues it may simply retard or stop the growth of
(free amino acids), followed by chromato- others.
graphic separation and UV-visible detection analytical methods Processes used to
for analytical purposes. analyze or characterize a mixture, a com-
amino acids A class of 20 naturally oc- pound, or an unknown material.
curring hydrocarbon molecules that combine anion A negatively charged ion (having
to form proteins in living things. They more electrons than protons).
include alanine (A), arginine (R), annual review An evaluation, conducted
asparagine (N), aspartic acid (D), cysteine at least annually, which assesses the quality
(C), glutamic acid (E), glutamine (Q), glycine standards of each drug product to deter-
(G), histidine (H), isoleucine (I), leucine (L), mine the need for changes in drug product
lysine (K), methionine (M), phenylalanine specifications or manufacturing or control
(F), proline (P), serine (S), threonine (T), procedures. [From FDAQSG]
tryptophan (W), tyrosine (Y), and valine (V). anodes Positive electrodes; negative
(Those are the so-called normal amino acids; ions (anions) migrate carrying electric cur-
others have been synthesized and are used in rent toward positive anodes.
medicinal chemistry.) They are incorporated antibody An infection-fighting protein
into proteins by transfer RNA according to molecule that tags, neutralizes, and helps
the genetic code. Amino acid analysis can be used to
amorphous Having no apparent shape or quantitatively determine the amount of
order; non-crystalline. protein and the proportions of amino
acids in a sample. The Waters UPLC
ampholyte An electrolyte that can be Amino Acid Analysis Solution is a
either positively or negatively charged, turnkey chromatographic system that
provides accurate, high-throughput
depending on the pH of its medium. amino acid analysis.
amphoteric A substance that has both
acid and base properties; amphoteric mol-
ecules can accept or donate protons to act as
an acid or a base.
ampule A small, sterile glass vessel with an
airtight seal that contains a single drug dose.
amyloid Insoluble fibrous protein ag-
gregates sharing specific structural traits.
Abnormal accumulation of amyloid in
organs may lead to amyloidosis and may
play a role in various other neurodegenera-
tive diseases.

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[ BIOTERMINOLOGY ]

destroy foreign microorganisms or toxins. sion vector.


Also known as immunoglobulins, antibod- aseptic Sterile, free from bacteria,
ies are produced by the immune system in viruses, and other pathogenic contaminants.
response to antigens. Asn Asparagine; one of more than 20
antifoam agent A chemical added to a naturally occurring amino acids.
fermentation broth to counteract the foam- Asp Aspartic acid; one of more than 20
ing (bubbles) that can be caused by mixing, naturally occurring amino acids.
sparging, or stirring. assay A technique (test) for measuring
antigen Any agent that reacts specifi- a biological response or for determining
cally with an antibody. Each antigen may characteristics such as composition, purity,
contain more than one site capable of activity, and weight.
binding to a particular antibody. (See ATD Arrival time distribution; mobility-
immunogen) separated ions show a spread of arrival
antigenicity The capacity of a substance times at the detector, dependent on their
to induce the formation of antibodies or to shape. The distribution of these arrival times
elicit an immune response when injected can be used to determine the differences in
into an animal. shape.
antisense oligonucleotides Antisense ATP Adenosine 5-triphosphate; helps
oligonucleotides interact with complemen- cells conserve and spend energy and often
tary strands of nucleic acids, modifying is used in assays of various ATP-dependent
expression of genes. enzymes.
API Active pharmaceutical ingredient; attenuated Weakened (attenuated)
the chemical entity that has the drug activity viruses can be used as vaccines; they can
and structure, but is not yet formulated with no longer produce disease but still stimulate
excipients. a strong immune response similar to the
aprotinin A polypeptide that inhibits natural virus. Examples include oral polio,
(blocks the action of) serine proteases. measles, mumps, and rubella vaccines.
aptamer Single-stranded RNA or AutoBlend In chromatography systems
double-stranded DNA molecules made up manufactured by Waters, AutoBlend mode
of short lengths of nucleic acids that form allows the automatic blending of up to
three-dimensional structures and can bind four buffers, salts, or solvents in accurate
to specific endogenous targets to produce its proportions reproducibly, which can simplify
biological action. mobile phase preparation. Any sequence of
aqueous solution A solvent solution isocratic, binary, ternary, and quaternary
made with water. gradients (very useful for SEC) can be used.
Arg Arginine; one of more than 20 The technique is useful for routine assays as
naturally occurring amino acids. well as automatic method development or
artificial chromosome DNA synthesized system flushing.
in chromosomal form for use as an expres- AutoBlend Plus AutoBlend Plus

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[ BIOTERMINOLOGY ]

technology extends the capabilities of amounts of a given protein through its natu-
AutoBlend by automatically managing pH ral method of replication, that is, injecting
and ionic strength requirements for the DNA into each cell.
mobile phase. The software calculates the baseline Observations or data used for
proportions of buffer stocks required for comparison or as a control.
desired conditions. Computation can be base pair Two bases on different strands
based on known pK values or on an empiri- of nucleic acid that join together. In DNA, cy-
cal calibration table, making any possible tosine (C) always pairs with guanine (G) and
buffer combination available. adenine (A) always links to thymine (T). In
autoradiography A technique that RNA molecules, adenine joins to uracil (U).
uses X-ray film to visualize radioactively basic variant A product variant that
labeled molecules or molecular fragments; exhibits a more positive charge character
used in analyzing the length and number by IEX or CE than the primary biotherapeu-
of DNA fragments after separation by gel tic form.
electrophoresis. batch A quantity of a drug substance
or drug product with uniform character and

B quality, within specified limits, produced ac-


cording to a single manufacturing run during
Bacillus subtilus A Gram-positive, the same cycle of manufacture.
aerobic, endospore-forming, rod-shaped batch culture Large-scale cell culture in
bacterium commonly found in soil, bodies of which cell inoculum is cultured to a maxi-
water, sewers, and in association with some mum density in a tank or airlift fermentor,
green plants; the second most common harvested, and processed as a batch.
species used in recombinant fermentation; benchtop A term used to distinguish
also known for its ability to handle organic between laboratory-scale or small-scale
waste in other types of biotechnology such processes, those that can be performed on
as bioremediation. the bench (in the lab or even on a tabletop)
bacteriophage A virus that infects and larger, pilot- or production-scale
bacteria, sometimes used as a vector. processes. Benchtop equipment (a benchtop
bacteriostatic agent A chemical agent bioreactor, for example) can fit on a table or
that prevents microbes from multiplying in a confined laboratory area.
but does not reliably kill them. May be beta sheet (-sheet) A structure result-
used during processing, in raw materials, ing from the regular, accordion-like folding
or in final products, especially multiple of polypeptide chains; the chief alternative
dosage medicines. to the alpha helix.
baculovirus A virus that replicates BEVS Baculovirus expression vector sys-
only in the cells of Lepidopteran insects; it tem; an insect cell culture method in which
has been genetically engineered to force a genetically engineered virus transfers re-
the insect cells in culture to produce large combinant DNA to the insect cells it infects,

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[ BIOTERMINOLOGY ]

that reaches systemic circulation, one of


the principal pharmacokinetic properties of
drugs.
biobetter A term for a follow-on
biologic that implies some improvement
on an existing biologic. This, and similar
terms, are not generally used by regulatory
authorities. (See biosimilar)
Biopharmaceutical development, manu- bioburden The number of contaminating
facturing, and analytical methods use a microbes (bacteria, yeast, mold, etc.) on or
variety of buffer solutions.
in a certain amount of material before that
which then produce the peptide or protein in material has been sterilized.
large quantities. bioburden assay Microbiological test
BFS Blowfillseal; a type of fill-and- that enumerates microbial content of a
finish system used in the pharmaceutical sample, but that is not validated to deter-
industry that forms a plastic container, mine sterility.
fills that container, and then seals it with bioequivalency The absence of a sig-
in-line machinery. nificant difference in the rate and extent to
BHK Baby hamster kidney cells; an estab- which the active ingredient or active moiety
lished mammalian cell line that is commonly in pharmaceutical equivalents or pharma-
used for biotechnology. ceutical alternatives becomes available at
bioactivity A proteins ability to function the site of drug action when administered at
correctly after it has been delivered to the the same molar dose under similar condi-
active site of the body (in vivo). tions in an appropriately designed study,
bioanalytical Sub-discipline of ana- Center for Drug Evaluation and Research
lytical chemistry covering the quantitative (2003), Guidance for Industry: Bioavail-
measurement of xenobiotics (drugs and ability and Bioequivalence Studies for
their metabolites, and biological molecules Orally Administered Drug Products
in unnatural locations or concentrations) General Considerations .
and biotics (macromolecules, proteins, biogeneric A term used for a biophar-
DNA, large molecule drugs, metabolites) in maceutical product that is produced and
biological systems. licensed by a different firm than the one that
bioassay Inoculation of an infective sub- originally licensed the molecule. A bioge-
stance into an animal to see if it develops neric is used for the same indications and
the same disease as a control animal; other may be produced by a substantially similar
analytical methods that use living cells, process, or one that is different, but results
tissues, or organisms as test subjects. in comparable product.
bioavailability Describes the fraction bioinformatics Use of computers in the
of an administered dose of unchanged drug life sciences: for instance, searching and

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[ BIOTERMINOLOGY ]

analysis of electronic databases of genomes not limited to) proteins and monoclonal
and protein sequences, and computer model- antibodies, peptides, and other molecules
ing of biomolecules and biologic systems. that are not chemically synthesized, along
biological activity The specific abil- with gene therapies, cell therapies, and
ity or capacity of a product to achieve a engineered tissues.
defined biological effect. Potency is the BiopharmaLynx Application Manager
quantitative measure of biological activity. for MassLynx Software; Software available
[From ICH Q6B] from Waters Corporation that automates
biologics Products of living organisms the data analysis and reporting of mass
used in the prevention or treatment of spectrometry data for peptide maps and
disease. intact mass measurements. It automatically
Biologics Price Competition and In- analyzes and assigns results, defining the
novation (BPCI) Act In 2009, the US sequence/features of known proteins, and
Congress passed the Biologics Price Compe- determining the ID of modified forms. Allows
tition and Innovation (BPCI) Act, authoriz- users to edit assignments, annotate new
ing FDA to oversee an abbreviated pathway peaks, and compare experimental samples
for approval of biologics that are biosimilar to a reference by using tabular and graphical
to already approved products. visualization tools.
biomarker In either small or large bioprocessing Using organisms or bio-
molecules, the presence or absence of an logically derived macromolecules to carry
enzyme, receptor, other protein or peptide, a out enzymatic reactions or to manufacture
mutated mRNA, or a genetic mutation, that products.
differentiates patient subpopulations and is bioreactor A vessel capable of sup-
indicative of a disease, the disease severity, porting a cell culture in which a biological
a stage in a disease, a subpopulation with transformation takes place (also called a
the disease that are differentiated by their fermenter or reactor).
drug response, or a subpopulation of people biosimilar A biopharmaceutical that
with a different drug activity or pharmaco- is produced using a different cell line or
kinetics. master cell bank and/or different process,
biomass The dry weight estimation of yet meets criteria for comparability in
organisms (usually microorganisms) in a clinical activity. A biosimilar may differ in
given habitat or medium. its purity/impurity profile, and its potency
biometabolism Physical and chemi- may differ in a definable way. (See also
cal processes that occur within a cell or an biogeneric, follow-on biological)
organismthe conversion of nutrients into biotechnology The industrial use of
energy, for example. living things, specifically genetically engi-
biopharmaceutical A therapeutic neered organisms.
product created through the genetic BLA Biologics license application; the
manipulation of living things, including (but required application for marketing a biologic

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[ BIOTERMINOLOGY ]

product in the United States. Most biotech- broth The contents of a microbial bioreac-
nology-derived drugs are approved through tor: cells, nutrients, waste, and so on.
a BLA, rather than an NDA, although some BSA Bovine serum albumin; a protein
biologics, such as recombinant insulin and derived from cow serum and commonly used
human growth hormone, considered to be as a growth additive for animal cell culture.
simpler in structure and well-characterized, BSE Bovine spongiform encephalopathy;
have been approved under NDAs. the TSE of cattle believed capable of cross-
blinding Clinical trial technique in which, ing the species barrier to have become feline
to eliminate bias in a research study, sub- spongiform encephalopathy (FSE) in cats,
jects (and sometimes clinical investigators) transmissible mink encephalopathy (TME) in
remain unaware of which therapeutic ap- farmed mink, and vCJD in human beings.
proach (for example, investigational product buccal delivery Transmucosal (across
or standard treatment) is provided. the mucosal membranes) drug delivery by
Blood-brain barrier To protect the way of the mouth.
brain from infection and from damage that buffer (buffering agent) A solution
could be caused by foreign chemicals, the containing a weak acid and a conjugate base
endothelial cell linings of its capillaries are of this acid; it resists change in pH near
tightly packed together. Nothing but water a specific value when an acid or a base is
and nutrients that are actively transported added to it because the acid neutralizes any
by cellular mechanisms can pass through. added base and vice versa. For example,
blotting Transfer of nucleic acids or bicarbonates and some proteins in biological
proteins from an electrophoresis gel strip fluids, when in solution, tend to stabilize the
to a chemically reactive paper or membrane hydrogenion concentration by neutralizing
(such as nitrocellulose paper) or matrix (within limits) both acids and bases so the
(nylon, for example) to which they bind. solution resists changes in pH.
Blotting is achieved through capillary bulk active ingredient Also bulk drug
diffusion (when the gel is placed between substance, the active ingredient that is for-
the paper or matrix and an absorptive pad) mulated with excipients to produce the drug
or through electrophoresis (electroblot- product formulation. Biopharmaceuticals are
ting). Of the three types of blots, Southern produced in bulk through bioprocessing.
hybridization (or Southern blot) transfers bulking agent An additive that in-
DNA; Northern blots transfer RNA, and creases the volume of a solution or a solid.
Western blots transfer proteins (also called
protein blots).
bolus A concentrated mass of injected C
medication. cake The solid sediment that has been
bond A mechanism through which atoms, compacted in a centrifuge after removal of
ions, or groups of atoms are held together as much liquid as possible; or the remaining
in a molecule. solid after completion of a lyophilization.

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calorimetry Analytical method that mea- bonded to a carbon atom; the carbon atom
sures heat loss or gain resulting from physical then has two additional bonds to attach to
or chemical changes in a sample. Differential the rest of the molecule.
scanning calorimetry compares the results of carcinogenic Cancer-causing; many
heating a sample to those for heating a refer- agents that are carcinogenic are mutagens
ence materialfor example, to measure the (agents that increase the occurrence of
temperature at which the sample crystallizes, mutation).
changes phase, or decomposes. cascade effects A series of events that
campaigned production Continuous result from one initial cause.
production of successive batches of the catabolites Waste products of catabo-
same product. lism, by which organisms convert substances
CAPA Corrective and preventive action; a into excreted compounds.
quality system defined by 21CFR 820.100; cation A positively charged ion (having
the policies, procedures, and support systems fewer electrons than protons).
that enable a firm to assure that exceptions CBE Changes being effected; a regulatory
are followed up with appropriate actions to submission sent to FDA to notify them of
correct the situation, and with continuous minor changes in a manufacturing process
improvement tasks to prevent recurrence and or its control. The sponsor is permitted to
eliminate the cause of potential nonconform- make the changes without waiting for FDA
ing product and other quality problems. response, and the changes become part of
[From FDAQSG] the existing licensed process. (See PAS)
capillary electrophoresis The minia- CBE-30 Changes being effected within 30
turized instrumental version of traditional days; a regulatory submission sent to FDA
electrophoresis using capillary column to request minor changes in a manufactur-
technology (that is, tiny fused-silica tubes ing process or its control. FDA has 30 days
with 20 to 100 m inner diameters) and in which to respond, after which the change
light-absorbance or fluorescence detection. is considered approved and the part of the
capsid The outer protein shell of a virus existing licensed process. (See PAS)
particle (virion). CBER Center for Biologics Evaluation
carbohydrates Molecules consisting of and Research at the FDA; CBER regulates
sugars. The basic carbohydrate units are vaccines, gene therapy, cellular products,
called monosaccharides, such as glucose, allergenic extracts, antitoxins, antivenins,
galactose, and fructose. Monosaccharides venoms, and blood and blood products (clot-
can be linked together into what are called ting factors and plasma derived products).
polysaccharides (or oligosaccharides) in CCD Charge-coupled device; semiconduc-
almost limitless ways. Oligosaccharides tors connected so that the output of one
contain a small number (typically three to serves as the input for the next (digital cam-
10) of component sugars. eras, video cameras, and optical scanners all
carbonyl bond An oxygen atom double- use CCD arrays); a light-sensitive integrated

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[ BIOTERMINOLOGY ]

CDER Center for Drug Evaluation and Re-


search; the largest of FDAs six centers, CDER
regulates prescription and over-the-counter
drugs. Following a transfer of responsibility
for biologics that began in June 2003, CDER
now also regulates therapeutic proteins and
monoclonal antibodies for in vivo use, which
were formerly regulated by CBER.
CE Capillary zone electrophoresis; an
Cell culture on the smallest scale uses analytical method in which a mixture is
petri dishes.
fractionated using charge; analytes are de-
circuit that stores and displays the data for tected using optical density, mass, or other
an image. physical properties. Also called CZE.
CCS Rotationally average collision cell bank A defined population of cells,
cross-section; The CCS of an ion is used such as an immortalized cell line, grown by
to calculate the area of an ion in the gas a defined process and cryopreserved in a de-
phase and expressed in Omega (see also fined process and within a defined passage
Omega). Omega can be calculated empiri- number range. The assumption is that each
cally through the measurement of an ions vial from a cell bank is comparable, and
drift time as it passes through a gas filled when thawed and added to a manufacturing
drift tube or travelling wave ion guide (see vessel (or an analytical assay), will perform
also TWIG). in a consistent way. (See master cell bank,
CD Circular dichroism; the absorption working cell bank)
of left and right circularly polarized light, cell banking Developing, reproducing,
a property of molecules that are optically aliquoting, and storing cells at a defined pas-
active. CD spectroscopy is a form of light- sage and homogeneity for particular uses.
absorption spectroscopy that measures cell culture Cells taken from a living
the difference in left and right circularly organism and grown in the lab (in culture).
polarized light absorbed by a substance. The Methods used to grow animal cells in the lab
spectra can be analyzed to learn the differ- are usually different from those used to grow
ent secondary structural types in a protein: microorganisms such as bacteria.
alpha helix, parallel and antiparallel beta cell lines When cells from the first
sheet, turn, and so on. culture (taken from the organism) are used
CDC Centers for Disease Control and to make subsequent cultures, a cell line
Prevention (Atlanta, GA); an agency of the is established. Thanks to genetic or other
Department of Health and Human Services. manipulations, immortal cell lines can
CDC develops and applies disease preven- replicate indefinitely.
tion and control, promotes environmental cellulose A fibrous polysaccharide mate-
health, and provides health education. rial, the main ingredient of plant cell walls.

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centrifugation Spinning samples at of a molecular entity; genetic and stability


high speeds, using centrifugal force (up to properties in the case of a cell line).
500,000 times the force of gravity) to sepa- charge The electrical state of an atom
rate substances with very small differences or molecule, whether positive, negative,
in density or weight. or neutral, according to the difference of
centrifuge A laboratory or industrial protons (positively charged) to electrons
apparatus that separates mixed samples of (negatively charged).
differing density by spinning them at high chelation The binding or holding of a
speed. metal ion (such as copper, zinc, cadmium,
certificate of analysis (COA) A batch- nickel, or cobalt) by another molecule or
specific document that is used to list test by another part of the same molecule; used
methods and results, including applicable in a form of affinity chromatography called
specifications, and a final batch disposition metal chelate chromatography.
CFR Code of Federal Regulations; the US chelator A molecule used to bind a metal
regulations that directly apply to biopharma- ion with more than one organic group to
ceutical development are in Title 21 parts form a highly stable structure.
58, 210, 211, and 600. Parts 50, 56, and chemical synthesis A non-biotech
312 apply to clinical trials. method of manufacturing chemicals, includ-
cfu Colony forming units; a measurement ing drugs.
of the number of microorganisms present chemostat A growth chamber that keeps
derived from the number of colonies that a bacterial culture at a specific volume and
form in a test culture. rate of growth by limiting nutrient medium
cGMP Current good manufacturing prac- and removing spent culture.
tice; see GMP. chimera Chimeric proteins (or fusion
change control A system by which proteins) are created through the joining of
changes to facilities, equipment, and two or more genes that originally coded for
processes are documented and approved. separate proteins.
The change control system ensures that chirality The condition of being chiral,
changes are evaluated and approved that is, a molecule in a configuration that
prior to implementation to maintain the is symmetrical with its mirror image; a
facilities, equipment, and processes in a right-handed chiral molecule rotates polar-
validated state. ized light rightward, a left-handed chiral
chaotropic Disrupting the structure of molecule rotates polarized light leftward.
water, macromolecules, or living systems to CHO cells Chinese hamster ovary cells; in
promote activities that would have been in- cell culture, the cells of a female hamsters
hibited by the water, molecules, or systems. reproductive organs, which historically have
characterization Precisely decipher- proven to be the basis for good expression
ing and describing an entitys properties systems in analytical studies and for produc-
(physical and chemical properties in the case ing pharmaceutical proteins.

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chromatography A technique used to centration of airborne particulate matter is


separate molecules based on how they tend controlled at specific limits to facilitate the
to bind to various solids, liquids, and gases; manufacture of sterile and high-purity prod-
based on the differential distribution of ucts. Clean rooms are classified according to
the substances between a stationary phase the number of particles per volume of air to
(sticky material such as silica gel or silicic meet standards of cleanliness. Contaminants
acid, usually contained in a column, tube, on surfaces and people entering and exiting
or capillary) and a gaseous or liquid mobile the room also are controlled.
phase (a medium that carries the sample clearance Clearancein volume/unit
through the stationary phase). This very timeof a drug or chemical from a body
effective technique can separate substances fluid, usually plasma or blood, by specified
that are nearly identical. route(s) and mechanism(s) of elimination,
chromophore A molecule that absorbs as indicated by a subscript (e.g., ClR, uri-
UV or visible light. nary clearance; ClH, hepatic clearance, etc).
chromosome A long and complex DNA ClT, total clearance, indicates clearance by
chain containing the genetic information all routes and mechanisms of biotransfor-
(genes) of a cell. Prokaryotes contain only a mation and excretion, operating simultane-
single chromosome; eukaryotes have more ously. ClT = kel Vd. Following intravenous
than one, made up of a complex of DNA, administration, ClT = D/AUC; following
RNA, and protein. The exact number of administration of drug by any route other
chromosomes is species-specific. Humans than the intravenous, ClT = F D/AUC.
have 23 pairs. clinical development The phases of
chymotrypsin A digestive enzyme that drug development during which a drug is
can cleave peptide bonds. tested in human subjects, also referred to as
CIP Clean-in-place; a way to clean large clinical trials.
vessels (tanks, piping, and associated clinical endpoint An indicator (such as
equipment) without moving them or taking blood pressure) measured in a human sub-
them apart, using a high-pressure rinsing ject to assess the safety, efficacy, or other
treatment, sometimes followed by steam-in- objective of a clinical trial.
place (SIP) sanitization. Chemically cleaning clinical hold Temporary cessation
and sterilizing equipment or systems without of a clinical trial by FDA if the agency is
removing them from their installed location. concerned about a drug or study protocol.
clarify To clear liquid of suspended The trial may resume when the problem is
particles through filtration, extraction/pre- solved.
cipitation, or centrifugation. clone To duplicate exactly, whether a
classical pharmaceuticals Small- gene or a whole organism; or an organ-
molecule, non-biotech drugs produced by ism that is a genetically identical copy of
chemical synthesis. another organism.
clean room A room in which the con- cloning vectors Methods of transferring

14 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

desired genes to organisms that will be used comparable Product made before and
to express them. Cloning vectors are used to after a given process change is comparable
make recombinant organisms. if the change is shown to have no adverse
CM Carboxymethylcellulose; a weak ion- effect on the key quality attributes of the
exchanger that is often coupled to a resin product, such as purity, potency, PK/PD,
used in charge based separation chromatog- stability, and safety. Small differences in,
raphy. It is a cation exchange resin. for example, the impurity profile are permit-
CMC Chemistry, manufacturing, and ted, as long as the function is not affected.
controls; the section of a BLA, NDA, or IND (See equivalent)
describing the composition, manufacture, comparability protocol A protocol that
and specifications of a drug product and defines the experiments and acceptance cri-
its ingredients. teria that will be used to evaluate a product
CMO Contract manufacturing organiza- before and after a process change, and if
tion; a company contracted to perform met, will provide documented evidence that
development and/or manufacturing services. the products are comparable.
codon A sequence of three nucleotide complaint Also customer complaint; any
bases in mRNA that specifies production of oral or written communication from an end
an amino acid or represents a signal to stop user of a medicinal product indicating that
or start a function. it had an adverse effect on a patient, did
colorimetry The measurement and not function as specified, or appeared to be
definition of unknown colors in terms of contaminated or defective in any way. The
standard colors; techniques may be visual, sponsor must promptly investigate all such
photoelectric, or spectrophotometric; colo- complaints and document the investigation
rimetry is useful in determining the concen- in a retrievable file. If the complaint is con-
tration of a chemical with color in a solution firmed, corrective and preventive actions are
by measuring the intensity of the color and required. Examples include FDA notification,
relating that intensity to the concentration of product lot(s) withdrawal, product recall, and
the solution. review of medical files of adverse events
column A vertical, cylindrical con- caused by the product. These requirements
tainer or vessel often used in separation are found in US regulations in 21 CFR 314,
processes such as extraction, distillation, the GCP regulations.
and chromatography. complement A group of proteins in
column aspect ratio The ratio of a the blood that work in concert with other
columns height to its diameter. immune system proteins and cells (such as
column chromatography A separation antibodies) in attacking foreign substances.
method in which the different components of component 1. Raw materials and compo-
a mixture migrate through a column at dif- nents (tubing, stoppers, vials, filters) having
ferent rates of speed based on their relative direct product contact during manufactur-
affinity for the stationary phase. ing, which are regulated under 21 CFR 84.

A Guide to the Biopharmaceutical Lexicon February 2012 15


[ BIOTERMINOLOGY ]

2. Differentiated from raw materials and bidden to distribute its products in interstate
excipients, which are chemical entities, and commerce, except for those products deemed
usually rated as lower in risk to patient and essential for the public health.
product quality. (Note: These terms may be contaminant A foreign agent or
used interchangeably or loosely, and defini- material that is not introduced as part of
tions vary between US, Europe, and WHO). processing, such as airborne particulates or
(See raw material, starting material, API) adventitious organisms.
concentration The amount of a particular continuous process verification An
substance in a given quantity of solution, alternative approach to process validation in
usually stated as a percentage by weight which manufacturing process performance is
or volume, as weight per unit volume, as continuously monitored and evaluated. [From
molarity (a one-molar solution contains one ICH Q8]
gram-mole of solute per liter of solution), or control group The group of subjects in a
as normality (a one-normal or one-molar so- controlled study that receives no treatment,
lution contains one gram-equivalent weight a standard treatment, or a placebo.
of solute per liter of solution). controlled delivery Drug delivery in
conformation The shape of a molecule, which the duration (sustained delivery)
produced by the specific spatial arrangement and/or the site (targeted delivery) of drug
of the units that compose it. release, action, and bioavailability are
consent decree Status imposed by controlled through various physicochemical
FDA on a company in serious violation of means designed to provide well-defined
federal regulations and related safety and pharmacokinetic profiles.
quality standards. A company must agree to Coomassie blue dye A sensitive stain
a series of measures aimed at bringing its for proteins used to visualize the bands in
manufacturing standards into compliance SDS-PAGE; also Coomassie brilliant blue.
with federal regulations. Until agreed-upon COS, CV-1 African green monkey kidney
conditions are met, a company may be for- cells, an established cell line that is com-
monly used for biotechnology.
cosmid An artificially constructed plas-
mid vector that contains a specific bacterio-
phage gene, which allows it to carry up to
45,000 base pairs of desired DNA.
cot1/2 DNA A curve that measures
genome complexity by determining the time
taken for half the DNA in a sample to rean-
neal (renature); it is measured for any new
Columns for bioseparations are avail- genome and compared to a standard such as
able in a wide variety of dimensions, the E. coli genome.
chemistries, and pore sizes to best meet
separation requirements. covalent bond Chemical bond in which

16 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

two atoms share one or more electron(s). cal or clinical pharmaceutical research.
Cp Process capability; a statistical cryoconcentration When a solution is
measurement of the relation between the frozen, water freezes as pure ice crystals.
observed variability of a process and the The remaining liquid therefore has a higher
specifications or requirements for individual solute concentration than the original
lots. Computed by dividing the range by the solution.
process variability (sigma); a larger number cryogranulation Use of a stream of
indicates a more capable process. liquid nitrogen to quickly create frozen,
critical micellar concentration (CMC) discrete pellets of a solution such as bulk or
The concentration of detergent at which final drug formulation.
micelles begin to form; from a practical cryopreservation Maintenance of frozen
point of view, the CMC defines the minimum cells, usually in liquid nitrogen.
concentration of free detergent that must C-terminal Carboxyl-terminal; the
be present to keep membrane proteins carboxyl terminus of a protein chain, with a
in solution. CMC values are affected by free carboxyl group.
temperature, ionic strength, pH, and buffer culture medium A complex mixture of
composition. The CMC is important in deter- organic and inorganic materials used as a
mining whether a detergent can be removed nutrient system for the cultivation of cells.
by dialysis. For example, a free detergent cuvette A transparent or translucent box-
molecule may pass through the membrane shaped container with precisely measured
but the largest micelle will not. (Compare dimensions for holding liquid samples to be
to CMC: chemistry, manufacturing, and put into a spectrophotometer; also such a
controls.) container with optical surfaces used to mold
critical process parameter An input samples so that their light-absorbing proper-
parameter (process setpoint) to a unit ties can be measured.
operation that must be tightly controlled Cys Cysteine; one of more than 20
by the operator, either manually or auto- naturally occurring amino acids.
matically, and which must be kept within a cytokine A protein that acts as a chemi-
specified range in order to produce output cal messenger to stimulate cell migration,
of acceptable quality within specifications. usually toward where the protein was
These parameters are identified during released. Interleukins, lymphokines, and
process development. interferons are the most common.
critical quality attribute A quality cytopathic Damaging to cells, causing
characteristic that must be controlled within them to exhibit signs of disease.
defined limits to ensure acceptable product cytoplasm The protoplasm of a cell
quality and performance. outside the nucleus (inside the nucleus is
CRO Contract research organization or the nucleoplasm). Protoplasm is a semi-
clinical research organization; a company fluid, viscous, translucent mixture of water,
contracted by a sponsor to perform preclini- proteins, lipids, carbohydrates, and inorganic

A Guide to the Biopharmaceutical Lexicon February 2012 17


[ BIOTERMINOLOGY ]

salts found in all plant and animal cells. delaminate To split apart into thin
cytostat Something that retards cellular layers; the act of separating a laminate
activity and production. This can refer to into layers.
cytostatic agents or to machinery, such as delivery matrix A heterogeneous
those that would freeze cells. semisolid matrix (such as a biopolymer gel)
cytotoxic Causing cell death. for the sustained delivery of drug substances
directly to the tissues; a matrix can be modi-

D fied to optimize the dosage or time period


during which the drug is delivered.
Da Dalton; the unit of molecular mass, denaturation A condition in which a
very nearly equal to that of a hydrogen protein unfolds or its polypeptide chains
atom (precisely equal to 1 on the atomic are disordered, rendering the molecule less
mass scale), named after John Dalton, who soluble and usually nonfunctional.
developed the atomic theory of matter denature To unfold a protein or break
(kDa, kilodalton). it up, changing its usual three-dimensional
DEAE Diethylaminoethyl; a weak ion- structure. Proteins can be denatured by
exchanger that is often coupled to a resin chemical action, heat, or even agitation of a
and used in charge based separation chro- protein solution.
matography. It is an anion exchange resin. denatured protein A protein having
deamidation Removal of one or more unfolded or disordered polypeptide chains,
amide groups from the Gln or Asn residue which render the molecule less soluble and
in a protein, converting the residues to Glu, usually nonfunctional. Sometimes a dena-
Asp, or isoAsp. Depending on the protein, tured protein can be refolded (renatured).
this may have no effect, or major effects, on derivatization A sampling technique;
potency, stability, or solubility. chemical conversion into a derivative form
Declaration of Helsinki A set of for identification purposes.
recommendations or basic principles guiding design space The multidimensional
medical doctors in the conduct of biomedical combination and interaction of input
research involving human subjects. variables (e.g., material attributes) and
deflashing The finishing procedure by process parameters that have been dem-
which excess plastic (flash) is removed from onstrated to provide assurance of quality.
a molding in BFS operations. Working within the design space is not
degradants The smaller parts that considered a change. Movement out of the
are left over after a molecule or solution design space is considered to be a change
degrades. and would normally initiate a regulatory
degradation Loss or reduction of post-approval change process. Design
quality, integrity, or character; a chemical space is proposed by the applicant and
reaction that breaks down a molecule into is subject to regulatory assessment and
smaller parts. approval. [From ICH Q8]

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[ BIOTERMINOLOGY ]

desorption The opposite of adsorption; dissociation constant A specific type


the release of adsorbed molecules, particles, of equilibrium constant that measures the
or cells into the surrounding medium. propensity of a larger object to separate
detergents Cleaning agents: chemicals (dissociate) reversibly into smaller compo-
with both hydrophobic (averse to water) and nents, as when a complex falls apart into its
hydrophilic (water-attracted) properties that component molecules, or when a salt splits
can dissolve fats and oils. up into its component ions. The dissociation
dialysis/diafiltration Membrane constant is usually denoted Kd and is the
ultrafiltration in which a large solute (such as inverse of the affinity constant. Dissociation
a protein) is washed or dialyzed with another constants are commonly used to describe
solution; for example, changing buffer condi- how tightly a ligand (such as a drug) binds
tions without affecting protein concentration. to a protein. Such binding is usually non-
diastereomer A stereoisomer (one of covalent, i.e., no chemical bonds are made
two or more molecules with the same atoms or broken. Since the binding is usually
in the same order but different three- described by a two-state process P + L = C
dimensional shapes) having two or more the corresponding dissociation constant is
chiral centers that is not a mirror image of defined Kd = [P][L]/[C] where [P], [L], and [C]
another stereoisomer of the same compound; represent the concentrations of the protein,
glucose, galactose, and mannose are all ligand, and bound complex, respectively.
diastereomers. The dissociation constant has the units of
differential scanning calorimetry molar (M), and corresponds to the concen-
Analytical method that independently tration of ligand [L] at which the binding site
measures the rate of heat flow to a sample on the protein is half occupied, i.e., when the
against a reference standard of the same concentration of protein with ligand bound
temperature. Data are obtained by monitor- [C] equals the concentration of protein with
ing the differential heat flow as a function no ligand bound [P]. The smaller the dis-
of temperature. DSC can measure heat sociation constant, the more tightly bound
capacities, phase transitions, dehydration, the ligand is; for example, a ligand with a
and heats of reaction. nanomolar (nM) dissociation constant binds
diluent A chemically inert substance more tightly than a ligand with a micromolar
added to a solution to increase the volume (mM) dissociation constant.
and reduce the concentration; a diluting disulfide bond A covalent bond formed
agent. between sulfur atoms of different cysteines
dimer A polymer made up of two identi- in a protein; such bonds (links, bridges)
cal molecules. When three monomers link contribute to the tertiary structure of the
up, the resultant polymer is called a trimer. protein.
Larger polymers are usually referred to by divalent cations Cations with a net posi-
placing a number before the -mer suffix: tive charge of +2.
4-mer, 5-mer, 6-mer, and so on. DIW Deionized water; very pure water in

A Guide to the Biopharmaceutical Lexicon February 2012 19


[ BIOTERMINOLOGY ]

can be cut from those sequences using


restriction enzymes. Fragments from various
samples can be analyzed to determine
whether they are from the same person. The
technique of analyzing restriction fragment
length polymorphism (RFLP) is called DNA
typing or DNA fingerprinting. It is also now
possible to detect polymorphisms consist-
ing of a single nucleotide. These are called
This is a simplistic model of the DNA single-nucleotide polymorphisms (SNP).
structure.
DNase Deoxyribonuclease, the enzyme
which contaminants have been ionized and that breaks up and destroys DNA sequences
removed by special filtration. (a protective mechanism in higher organisms).
DMPK Drug Metabolism and Pharmaco- DNA sequencing Determing the order of
kinetics. Determining the DMPK properties nucleotide bases in a DNA molecule.
of a drug allows the drug developer to DNA vaccine A nucleic acid vaccine:
understand the safety and efficacy data Genes coding for specific antigenic proteins
required for regulatory approval. are injected to produce those antigens and
DMSO Dimethyl sulfoxide; a common trigger an immune response.
cryoprotectant used to cryopreserve cells DOE Design of experiments; a term for
and tissues. experiments that are planned and analyzed
DNA Deoxyribonucleic acid; the nucleic using statistical design tools. A structured,
acid based on deoxyribose (a sugar) and the organized method for determining the
nucleotides G, A, T, and C. Double-stranded relationship between factors affecting a
DNA has a corkscrew-ladder shape (the dou- process and the output of that process.
ble helix) and is the primary component of [From ICH Q8]
chromosomes, which thus carry inheritable dosage group A group of subjects in a
characteristics of life. (See nucleotides, clinical trial receiving the same dosage of a
nucleic acids) drug being tested.
DNA array Spots of DNA, oligonucle- downstream processing Bioprocess-
otide, or cDNA arranged on a solid support ing steps following fermentation and/or
such as a glass or silicon DNA chip (or cell culture, a sequence of separation and
microarray), which is used for screening, purification activities needed to obtain the
sequencing, genetic mapping, and so on. required drug product at the necessary level
DNA fingerprinting Sequences of of purity.
nucleic acids in specific areas (loci) on a DQ Design qualification; a documented
DNA molecule are polymorphic, meaning review of the design, at an appropriate stage
that the genes in those locations may differ of stages in the project, for conformance to
from person to person. DNA fragments operational and regulatory expectations.

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[ BIOTERMINOLOGY ]

drift time The drift time of an ion is ion is modeled by a collection of overlap-
a measure of how long it takes to move ping hard spheres with radii equal to hard
through a mobility region in a mass sphere collision distances (see also PA). The
spectrometer. For a travelling wave, this is orientationally averaged momentum transfer
measured in low hundreds of milliseconds cross section is calculated by determining
(see also TWIG). the scattering angles between the incoming
drug discovery Methods for identify- buffer gas atom trajectory and the departing
ing new therapeutic molecules. High- buffer gas atom trajectory.
throughput techniques include combinato- elastomeric closure A rubber or rubber-
rial chemistry, genomics, and proteomics like closure or stopper; a packaging component
analysis as the starting point. Low- that may come into direct contact with the
throughput methods include traditional enclosed drug, which is usually an injectable.
disease research. electrolytes Ionized salts in body fluids;
drug product The final dosage form of electrolyte solutions are solutions containing
a pharmaceutical medicine containing drug charged atoms or molecules.
substance formulated with selected excipi- electroosmotic The movement of a liquid
ents and packaged for the end user. out of or through a porous material or a
drug substance The active drug chemical biological membrane under the influence of
or biological substance in purified bulk form. an electric field.
The drug substance is further processed to electrophoresis Analytical method
derive a drug product. Also known as active in which an electric field is applied to a
pharmaceutical ingredient (API). medium (paper, thin-layer plates, polyacryl-
amide or agarose gel), causing charged

E molecules to move through it. In capillary


electrophoresis, samples move through
EBA Expanded-bed adsorption; a chroma- a buffer-filled tube (capillary). In gel
tography method that uses an upward flow electrophoresis, samples move through a
of liquid in a column of suspended, dense thin agarose or polyacrylamide gel. Bigger
chromatography beads to allow passage biomolecules (and those carrying few
of crude, unclarified raw materials without Electrospray ionization is used to transfer
clogging the chromatography medium. analytes from liquid to a gaseous phase in
an ionized form.
efficacy The ability of a substance
(such as a protein therapeutic) to produce
a desired clinical effect; its strength and
effectiveness; usefulness; the power to
produce an effect.
efficiency of delivery The relative ef-
fectiveness of a drug delivery system.
EHSS exact hard sphere scattering; An

A Guide to the Biopharmaceutical Lexicon February 2012 21


[ BIOTERMINOLOGY ]

electrically charged chemical groups) move elution volume The amount of eluent
slower through the medium than smaller that passes through the column in column
molecules (and those with many electrically chromatography before a particular peak
charge chemical groups). appears in an elution profile (that is, before
electrospray ionization Technique a specific substance of interest comes out
for generation of charged ions for mass with it). Also, the volume during which a
spectrometry. Analyte containing solution particular compound is eluted.
is dispersed as a fine charged aerosol into EM Electron microscopy; in which
the MS by passage of the liquid through a instruments focus electrons like optical
electrically charged capillary emitter. microscopes focus light. Scanning electron
electrostatic binding A chemical bond microscopy (SEM) and transmission electron
of two atoms or molecules by an electro- microscopy (TEM) are sometimes used in
static force (like static electricity) caused bioanalytical laboratories.
by one or more electrons moving from one EMA European Medicines Agency; the
atom to the other. agency responsible for regulating biophar-
elimination The rate at which drugs are maceuticals in the European Union.
removed from the body. emulsification A process that creates a
ELISA Enzyme linked immunosorbent stable mixture of two liquids that normally
assay; a test to measure the concentration would not mix together (such as oil and
of antigens or antibodies. water) by forcing one to disperse in the other
eluate Also called elution fractions; as droplets.
the separated components of a mixture that enantiomer Either of a pair of chemical
wash out from a chromatography column compounds whose molecular structures have
during elution. a mirror-image relationship to each other
eluent The substance used to recover (see diastereomer).
samples from a chromatography column; encapsidation During formation of a
sometimes an elution solvent. When a buff- virus particle, the process by which nucleic
ering agent is used, it is called an elution acid is incorporated (encapsidated) into the
buffer. Sometimes a solvent is used and just viral capsid. (See also capsid)
referred to as the eluent. encapsulation To enclose in a capsule,
elution Washing out; removing adsorbed usually one made of a biodegradable
material with a solvent or buffering agent. polymer.
elution profile A graph made to show how endogenous Growing or developing from
much material is being carried out of the col- a cell or organism, or arising from causes
umn by the eluent in column chromatography within the organism.
over time. The graph will show a number of endonuclease A restriction enzyme that
different peaks; each peak represents a differ- breaks up nucleic acid molecules at specific
ent separated material from the original mixed sites along their length. Such enzymes are
substance. Also called a chromatogram. naturally produced by microorganisms as a

22 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

defense against foreign nucleic acids. viables and non-viables via standardized
endoplasmic reticulum A highly sampling methods performed at established
specialized and complex network of branch- time intervals.
ing, interconnecting tubules (surrounded enzymes Proteins that catalyze bio-
by membranes) found in the cytoplasm chemical reactions by causing or speeding
of most animal and plant cells. The rough up reactions without being changed in the
endoplasmic reticulum is where ribosomes process themselves.
make proteins. It appears rough because epithelium (epithelial) The layer(s) of
it is covered with ribosomes. The smooth cells between an organism or its tissues or
endoplasmic reticulum is the site for organs and their surrounding environment
synthesis and metabolism of lipids, and it (skin cells, inner linings of lungs or digestive
is involved in detoxifying chemicals such as organs, outer linings of kidneys, and so on).
drugs and pesticides. epitope A molecular region on the
endotoxin A poison in the form of a fat/ surface of an antigen that elicits an
sugar complex (lipopolysaccharide) that immune response and can combine with
forms a part of the cell wall of some types the specific antibody produced by such a
of bacteria. It is released only when the cell response; also called a determinant or an
is ruptured and can cause septic shock and antigenic determinant.
tissue damage. Pharmaceuticals are tested equivalence Two lots of product are
routinely for endotoxins. equivalent if, within experimental error,
engineering batch A batch run at the they are essentially equal in purity/impu-
defined cGMP production scale for the pur- rity, potency, identity, and safety. A more
pose of evaluating the performance of any or stringent requirement than comparability.
all of the unit operations prior to initiating (See comparable)
cGMP manufacturing. It is not intended to be Escherichia coli Bacteria normally
released as a fully compliant cGMP batch. An found in the intestinal tract and widely
engineering batch may be executed using a used in biochemical and genetic studies and
batch record, but need not comply with all genetic engineering. E. coli is often used as
instructions and requirements. a vehicle for combining a segment of DNA
enthalpy Heat content; enthalpy change with an unrelated segment, creating con-
of a chemical reaction equals the difference tinuous DNA that does not occur naturally
between the heat put into breaking bonds (recombinant DNA).
and the heat released by new bond forma- eukaryotes Complex organisms, often
tion. multicellular, whose cells contain nuclei.
environmental monitoring A docu- exception A deviation from approved
mented series of sampling and testing GMP procedure; an out-of-specifications
performed on controlled environments to result or unexpected or out of trend result;
assure compliance with room classifications. a customer complaint. Exceptions must be
Testing typically includes monitoring of detected, investigated, and managed using

A Guide to the Biopharmaceutical Lexicon February 2012 23


[ BIOTERMINOLOGY ]

quality systems such as CAPA (corrective (such as the medicinally active components
and preventive action). of plant or animal tissue) by a physical
excipient A type of raw material that or chemical process. 2. Materials that
is present in the drug product and thus are actually removed from a container or
has direct patient contact; includes inert closure by a given formulation or product.
materials such as bulking agents, stabiliz- (See leachables)
ing agents, preservatives, salts, solvents, extraction Liquid-liquid extraction is
or waters. An excipient must be evaluated a process in which a solute is removed
for safety in animals, unless it has been ap- from a liquid by transferring the solute
proved as GRAS or is on a list of approved into a second liquid phase. The two liquid
excipients. phases must be insoluble with each other.
exclusion limit In size-exclusion (or gel Separation is based on different solu-
filtration) chromatography, the smallest size bilities of the solute in the two phases.
or dimension of molecule that is too large to Extraction is gentle and suitable for
enter the pores on gel particles. unstable molecules.
excretion The elimination of substances extrusion A process of forming rods,
from the body. In rare cases, some drugs tubes, or other continuously formed
irreversibly accumulate in body tissue. pieces by pushing hot or cold semisoft
exogenous Developing from outside, solid material through a die; also any
originating externally. Exogenous factors process of pushing a substance through
can be external factors such as food and holes or a tube.
light that affect an organism.
express To translate a cells genetic
information, stored in its DNA (gene), into a F
specific protein. Fab Antigen-binding fragment of an
expression system A host organism immunoglobulin. An IgG Fab is prepared by
combined with a genetic vector (such as a enzymatic cleavage of the intact tetrameric
virus or circular DNA molecule called a plas- IgG, and reduction of the inter-chain disul-
mid) that is loaded with a gene of interest. fide links, and binds one mole of antigen per
The expression system provides the genetic mole. [See F(ab)2]
context in which a gene will function in the F(ab)2 Dimeric antigen-binding frag-
cellthat is, the gene will be expressed as ment of an immunoglobulin. An IgG F(ab)2
a protein. is prepared by enzymatic digestion of the
expression vector A virus, plasmid, intact IgG, which removes the Fc portion of
cosmid, or artificial chromosome that the molecule. F(ab)2 binds two moles of
delivers foreign genes to a host, creating a antigen per mole. (See Fab)
recombinant organism that will express the FAb Antibodies are Y-shaped molecules.
desired protein. The arms of each Y are the FAb regions
extractables 1. Substances withdrawn (fragment antigen binding sites) that bind

24 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

to antigens; the stem of the Y is the Fc Administration.


region, which attracts microbe-engulfing FDA-483 A form prepared at the conclu-
cells to destroy what has been bound. If the sion of an inspection (without review by FDA
active part of an antibody can be identi- management) citing observations that may
fied, sometimes only that part of it may be constitute violations of law, in the opinion of
needed as a therapeutic molecule (facilitat- the inspector. Originally intended to inform
ing production and processing by reducing companies of possible product adulteration so
the size and lessening the chances of an that prompt corrective action could be taken,
immune response in patients who receive the 483s now list a host of observations. Ac-
drug). This fragment may be conjugated to cessible through the Freedom of Information
another molecule (such as PEG) for stability Act by competitors, potential customers, and
or other reasons. the media, 483s can lead to withholding of
factors (coagulation factors) Protein product approvals, may come into play in due
constituents of blood, numbered according diligence phases of acquisitions and mergers,
to the order in which they were discovered, and can potentially cost companies money.
which separate out in a traditional fraction- FDAMA FDA Modernization Act; enacted
ation procedure (Cohn fractionation); Factor in November 1997, this amends the FD&C
VIII, for example, is a blood serum protein Act to improve (facilitate) the regulation of
involved in clot formation that is also called food, drugs, devices, and biological products.
antihemophilic globulin. feedstock Also feed or feed stream; most
Fc Portion of an immunoglobulin often the raw broth containing particles to be
molecule that carries various effector removed that is placed into a laboratory or
functions, such as the ability to bind manufacturing appliance such as a centrifuge
complement. Important in immunological or chromatography column.
activities, and separable from the antigen- feed stream Also feed or feedstock;
binding portion by enzymatic or chemical most often the solution fed into a reaction or
cleavage. (See Fab) separation/purification process.
FD&C Act Food, Drug and Cosmetic Act of fermentation Large-scale cultivation of
1938; the major legislation regulating such microorganisms or single-celled creatures
products in the United States. It requires for industrial purposes, such as to produce
companies to prove that their products are therapeutic molecules or specialty foods
safe before marketing them, extends FDA and beverages.
oversight to cosmetics and therapeutic fermenter A large bioreactor used to
devices, explicitly authorizes factory inspec- grow bacteria or fungi in liquid culture.
tions, requires standards for food, and adds fill-and-finish The part of a manufactur-
injunctions to previous penalties of seizure ing process concerned with packaging a
and criminal prosecution for violations of product in its final form.
related laws. filter Porous material through which a
FDA United States Food and Drug liquid or gas is passed so that particulates

A Guide to the Biopharmaceutical Lexicon February 2012 25


[ BIOTERMINOLOGY ]

FMEA Failure modes evaluation and


analysis; a method used to perform risk
assessment and risk mitigation. A unit
operation is analyzed, and all the potential
modes by which it might fail are mapped out.
Then a control strategy is defined to reduce
the probability that a given mode of failure
will occur. Used in the aerospace and other
industries with much success. (See also
Liquid formulations are most common HACCP)
for biopharmaceuticals.
folding A process in which a protein
and impurities are held in suspension and spontaneously forms into its correct, knotted
removed from the feed stream. Some impuri- tertiary structure that is held in place by
ties may pass through. chemical bonds and by attractive forces
filtrate The part of a mixture that passes between atoms.
through a filter, also called permeate. follow-on biologic Another term for
filtration Separation of solid particles biosimilar or biogeneric.
from a fluid by passing the mixture through a for-cause inspection An FDA facility
porous, fibrous, or granular substance. inspection carried out because of specific
FISH Fluorescence in situ hybridization; information such as the results of a sample
an analytical method in which specific se- analysis, observations made during previous
quences of DNA are labeled with fluorescent inspections, product recall or market with-
molecules, hybridized (amplified), and then drawal, consumer or employee complaint,
detected with a fluorescence microscope. adverse reaction report, or suspicion of
floc A fluffy aggregate that resembles a fraud. Also, a similar inspection of a clinic
woolly cloud. or an IRB.
flocculant A precipitate (floc), some- forced degradation Also known as
times a flaky or fluffy aggregate that accelerated degradation, a process whereby
resembles a woolly cloud; the aggregation the natural degradation rate of a product or
(flocculation) of initially separate cells that material is increased by the application of
form flocs. an additional stress to rapidly screen mate-
flux Usually, the rate of flow. A lower rial stabilities.
flux means slower flow, usually caused by formal experimental design A struc-
clogging. tured, organized method for determining
fMet N-formyl methionine; a variant the relationship between factors affecting
of the amino acid methionine that many a process and the output of that process.
bacterial cells can produce. In mammals, Also known as design of experiments.
fMet results in a strong adverse reaction by [From ICH Q8]
the body. formamide A colorless, oily, hygro-

26 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

scopic liquid used to denature nucleic radiation: How much is absorbed at each
acids and as a solvent, softener, or chemi- wavelength indicates the types of chemical
cal intermediate. bonds present in the molecules of the
formic acid The simplest carboxylic sample. The Fourier-transformation is a
acid, miscible with water and most polar mathematical method used to interpret the
organic solvents, and somewhat soluble vibrations of functional molecular groups
in hydrocarbons. It is used in laboratories and highly polar bonds. FT-IR produces a
as a solvent modifier for HPLC separations fingerprint illustrating the vibrational
of proteins and peptides, especially when features of all sample components.
the sample is being prepared for mass functional genomics A method of se-
spectrometry analysis. lecting among the thousands of drug leads
formulation The method and process that can come out of discovery efforts.
of selecting the components of a mixture; Whereas genomics studies the genetic
the product of such a process; the form in basis of organisms and their diseases,
which a drug is given to patients (tablets functional genomics challenges drug lead
or injections, for example); developed in candidates derived from genomic studies
concert with a drug delivery system and with early development-style assays to
targeting mechanism needed to get the build as much information as possible
active ingredient to its site of action. about the potential drug into the discovery
fraction A separate portion of a mix- process.
ture, often used to describe the part that fusion partner When making a small
contains a particular molecular species. protein or peptide in E. coli, it is often
fractionation range The range of necessary to produce the protein fused
molecular sizes that can fit (or diffuse) to a larger protein to get high levels of
into the pores of a gel filtration chroma- stable expression. The resulting fusion
tography medium particle. protein must be cleaved (chemically or
free radicals Short-lived, highly reactive enzymatically) to yield the desired protein
molecular fragments that are often capable or peptide. The non-product fusion partner
of initiating/continuing chemical reactions is left over and usually thrown away.
by means of a chain reaction mechanism. fusion protein A protein containing
They are usually formed by the splitting amino acid sequences from each of two
of molecular bonds, which requires energy distinct proteins. It is formed by expres-
input. Free radicals act as initiators or sion of a recombinant gene in which
intermediates in oxidation, combustion, two coding sequences have been joined
polymerization, and photolysis. together. Typically, this is accomplished by
FT-IR Fourier transform infrared cloning a cDNA into an expression vector
spectroscopy; an analytical method that in frame with an existing gene.
measures the ability of a sample to
absorb different wavelengths of infrared

A Guide to the Biopharmaceutical Lexicon February 2012 27


[ BIOTERMINOLOGY ]

G
gas chromatography Analytical method
gene therapy, the parents egg and sperm
cells are changed with the goal of passing
on the changes to their offspring.
in which a volatile substance to be separated genetic engineering Altering the
is introduced into a stream of nonreactive genetic structure of an organism (adding
gas or other stationary phase. For example, foreign genes, removing native genes, or
in capillary gas chromatography, the gas both) through technological means rather
mixture moves through a tube coated with than traditional breeding.
liquid, and how fast it moves through the genetic polymorphisms Gene altera-
tube depends on the degree to which it stays tions, additions, omissions, or deletions that
in the nonreactive gas or dissolves in the alter biologic functioning or changes in drug
liquid (partitioning). metabolism.
GCP Good clinical practice; according genome The collection of all the genes
to 21 CFR Parts 56, 312, and 314, the for an organism.
regulations that govern the actions and genomics Study of the genetic make-up
environment of those working in clinical of organisms, including sequencing and
testing of drugs and medical devices on mapping of their DNA. The Human Genome
human beings. These regulations include Project was a government-coordinated
rules for obtaining informed consent and effort of many genomics researchers who
data integrity requirements. sequenced and mapped the entire human
gene The unit of inheritance consisting genome.
of a sequence of DNA occupying a specific genotoxicity Ability of a substance to
position within the genome. Three types of damage the genome.
genes have been identified: structural genes genotoxin A substance that causes dam-
encoding particular proteins; regulatory age to an organisms DNA.
genes controlling the expression of the genotype The genetic composition
other genes; and genes for transfer RNA or of an organism (including expressed and
ribosomal RNA instead of proteins. non-expressed genes), which may not be
gene therapy Treats, cures, or prevents readily apparent. Compare to phenotype,
disease by changing the expression of a the outward characteristics that result from
persons genes or inserting genes into the gene expression.
genome. In its infancy, current gene therapy germ cell The sex cells in higher
is primarily experimental, with most human animals and plants that carry only half of
clinical trials only in the research stages. the organisms genetic material and can
Gene therapy can target somatic (body) combine to develop into offspring.
or germ (egg and sperm) cells. In somatic glass state The amorphous solid that,
gene therapy, the recipients genome is for example, contains the therapeutic protein
changed, but the change is not passed in lyophilization; any material that takes
along to the next generation. In germ-line the shape of its container and is formed

28 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

by cooling a liquid until it is rigid but not


crystallized.
Gln Glutamine; one of more than 20
naturally occurring amino acids.
GLP Good laboratory practices; ac-
cording to 21 CFR Part 58, regulations to
ensure quality of nonclinical laboratory
studies related to safety. All activity is
recorded, trained staff uses only established
procedures, and records and samples are GLPs provide guidance on the best
maintained. practices for laboratory activities, from
Glu Glutamic acid; one of more than 20 research techniques to records and
documentation.
naturally occurring amino acids.
glucose A monosaccharide (or simple equipment must be qualified, and properly
sugar) is an important carbohydrate in trained staff must maintain a clean/sterile
biology. The living cell uses it as a source of environment.
energy and metabolic intermediate. Golgi body A cell organelle consisting of
Gly Glycine; one of more than 20 natu- stacked membranes where posttranslational
rally occurring amino acids. modifications of proteins are performed;
glycan Refers to a polysaccharide or also called Golgi apparatus.
oligosaccharide that can be found at- Grams stain/Grams method A method
tached to proteins as in glycoproteins and developed by Hans C.J. Gram for identifying
proteoglycans. bacteria. Bacteria are stained with gentian
glycoproteins Proteins that contain sugar violet, then treated with Grams solution
side chains added as a posttranslational (water, potassium iodide, and water) and
process; presence of sugar side chains often counterstained. They are then treated with
affects activity and in vivo stability. alcohol and washed with water. Gram-nega-
glycosylation Adding one or more tive bacteria do not retain the purple dye (E.
carbohydrate molecules onto a protein (a coli, for example); Gram-positive bacteria do
glycoprotein) after it has been built by the retain the purple dye (Staphylococcus aureus,
ribosome; a post-translational modification. for example).
GMPs Good manufacturing practices; GRAS Generally recognized as safe; a
according to 21 CFR Parts 210, 211, 600, special status afforded by FDA to ingre-
610, and (for devices) 820, current good dients and methods that have a proven,
manufacturing practices (cGMPs) influence longstanding history of causing no harm to
the manner in which biopharmaceuticals and humans or animals.
other drugs and medical devices are pro- growth hormone A protein produced in
duced. Standard operating procedures must the pituitary gland to control cell growth.
be followed, processes must be validated, Guidance for Industry The next regula-

A Guide to the Biopharmaceutical Lexicon February 2012 29


[ BIOTERMINOLOGY ]

tory level up from a Points to Consider Waters MS Technology that couples high-
(PTC) document (and below official Code of efficiency ion mobility separations (IMS)
Federal Regulations law). with time-of-flight (TOF) mass analysis.
GXP All-inclusive term for GCPs, GLPs, HDMS provides an additional dimension
and GMPs. of information for separations, providing
additional details on glycopeptide, protein,

H and polymers such as PEG that are conju-


gated to proteins, including determining
HACCP Hazard analysis and critical partial sequence information of proteins,
control points analysis; a method used to and differentiating by size and shape, as
perform risk assessment and risk mitigation. well as mass.
Each unit operation is evaluated to define HeLa Human cervical cancer cells; an
what critical parameters must be kept within established cell line that is commonly used
specified ranges, and the process control in biotechnology.
strategy is designed to monitor and control hemocytometer A device for counting
within that range. Used in the food industry blood cells.
with much success. (See also FMEA) hemoglobin A complex protein (a 4-mer)
half-life (t1/2) Time required to de- in red blood cells that binds and releases
crease the amount of drug in body by 1/2 oxygen, carrying it from the lungs to all
during elimination (or during a constant other tissues.
infusion). HEPA filtration High-efficiency particu-
hapten A small, separable part of an late air filter used to remove contaminants
antigen that reacts specifically with an
antibody but is incapable of stimulating Visualization of a complex population
of PEG structures by HDMS.
antibody production except in combination
with a carrier protein molecule.
harm Physical injury or damage to the health
of people, or damage to property or the environ-
ment. [From ISO 14971; see also ICH Q9]
hazard The potential source of harm
[From ICH Q9; see also ISO/IEC Guide 51].
HCIC Hydrophobic charge induction chro-
matography; a type of HIC that is based on
pH rather than salt concentration, allowing
for elution under relatively mild conditions
and eliminating the requirement for an as-
sociated filtration step in early separations.
HDMS (IMS-TOF MS) System High
Definition Mass Spectrometry (HDMS);

30 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

or to prevent particles from entering a clean cloned substances.


room. host cell protein(s) (HCP) Proteins
heterogeneity A term used to describe a from the host cell system used to manufac-
biological component (i.e. protein) consisting ture a biopharmaceutical drug. Host cells
of multiple structural variations. contain hundreds to thousands of host cell
HGH Human growth hormone; an early proteins and other biomolecules that could
biopharmaceutical. Formerly derived from contaminate the final product.
cadaveric pituitary glands, this protein is HPLC High-performance liquid chroma-
now produced by recombinant expression. tography or high-pressure liquid chromatog-
HIC Hydrophobic interaction chroma- raphy; a form of liquid chromatography in
tography; a type of liquid chromatography which a sample is forced at high pressure
that makes use of the relative solubility of through a tube (column) that is packed
proteins and matrix materials. Hydrophobic tightly with chromatographic media.
interactions are strongest at high ionic human genome The complete set of
strengths, so salt is usually included to human genetic instructions.
increase those levels. hybridization The process of joining
high-throughput screening Robotic complementary strands of DNA to make
methods used to sort through thousands of an RNA-DNA hybrid; the partial pairing of
chemical compounds by running assays on DNA single strands from genetically differ-
many at a time. ent sources.
Higher Order Structure (HOS) Struc- hybridoma An immortalized cell line
ture relating to secondary, tertiary, or (usually derived by fusing B-lymphocyte
quaternary structure of a biomolecule, in cells with myeloma tumor cells) that
contrast to its primary structure, the amino secretes desirable antibodies.
acid sequence. Hydrogen Deuterium Exchange (HDX)
His Histidine; one of more than 20 Hydrogen deuterium exchange (HDX) with
naturally occurring amino acids. mass spectrometry (MS), also referred
histochemistry A science that combines to as HX MS, is an important structural
the techniques of biochemistry and histol- characterization tool for discovery and de-
ogy to deal with the chemical changes and velopment stages. Uses in biotherapeutics
chemical constitution of tissues. include epitope mapping, binding, and pro-
hit In drug discovery, a positive result in a teindrug interaction studies, aggregation
high-throughput assay. studies, effect of mutation on conforma-
hormone A protein released by endocrine tion, and localization of conformational
glands or sex organs to travel in the blood changes. HDX provides information on
and act on tissues at another location in the the relative deuterium uptake of different
body. conformations of a protein, or locations
host A cell or organism used for growth within a protein.
of a virus, plasmid, or for the production of hydrolysis Literally cleaved by water,

A Guide to the Biopharmaceutical Lexicon February 2012 31


[ BIOTERMINOLOGY ]

a reaction in which the chemical bond


attaching an atom or group of atoms to the
rest of a molecule is severed, followed by
attachment of hydrogen at the same point.
Most often in biopharmaceuticals, the break-
age of peptide bonds by addition of a water
molecule.
hydrophilic Having an affinity for water;
attracting, dissolving in, or absorbing water;
Insulin, a hormone, was the rst bio-
readily absorbing moisture; having strongly pharmaceutical approved by the FDA.
polar molecular groups that readily interact
with water. lel unbiased approach to data acquisition
hydrophobic Insoluble in water; the that increases both the number of peptides
extent of insolubility; not readily absorbing and also the reproducibility of the peptides
water; resisting or repelling water, wetting, sampled during an LC/MS experiment.
or hydration; or being adversely affected by The database search algorithm is for the
water. qualitative identification of data originating
hydrophobicity The lack of an affinity from LC/MS E data, whereby multiple precur-
for water. sor ions are fragmented simultaneously.
hygroscopic Ready to take up and retain Properties that are used by the algorithm
moisture. include retention time, precursor and prod-
uct ion intensities, charge state, as crucially

IJ the accurate masses of both the precursor


and product ions form the LC/MS E data.
ICH The International Conference on IEC Ion-exchange chromatography; some-
Harmonisation of Technical Requirements times abbreviated IEX, a liquid chromato-
for Registration of Pharmaceuticals for graphic technique based on the electrical
Human Use; a project bringing together the phenomenon of ion exchange. The amphoter-
regulatory authorities of Europe, Japan, and ic nature of proteins can be exploited to bind
the United States with experts from the phar- them in cation-exchange (binding positively
maceutical industry to discuss scientific and charged proteins) or anion-exchange (bind-
technical aspects of product registration. Its ing negatively charged proteins).
purpose is to recommend ways to harmonize IEF Isoelectric focusing; analytical
the technical guidelines and requirements for separations in an electrical field through
product registration and reduce or obviate a pH gradient (therefore based on the net
the need to duplicate testing during develop- charge of the molecules); usually done in
ment of new medicines. bioanalysis at a neutral pH so that proteins
Identity E System A database search (for example) will move under the influence
strategy for LC/MS E data. LC/MS E is a paral- of the electric field until their net charge

32 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

is zero (their isoelectric point, pI). cIEF is a molecule.


specialized form of electrophoresis that can in vitro Performed using laboratory ap-
be adapted to the capillary format. paratus rather than a living animal.
IEX See also: IEC, ion-exchange in vivo Involving living animals or
chromatography. humans as test subjects.
Ile Isoleucine; one of more than 20 inclusion bodies Discrete structures
naturally occurring amino acids. (virions, viral components, cellular material,
immortalize To alter cells (either aggregated proteins) present either normally
chemically or genetically) so that they can or abnormally within cells.
reproduce indefinitely. IND Investigational New Drug application;
immunoassay An antibody-based test process by which a company files a request
used most often for bioanalytical purposes. with FDA for permission to expose its experi-
immunodetection A process that mental drug to patients or healthy human
identifies and quantifies specific biological volunteers. This application must be filed
substances, such as antigens. for each individual clinical study performed,
immunogen A substance that provokes Phases 1 to 3.
an immune responsethat is, the body indications A collection of symptoms or
recognizes it as a foreign agent that must be one disease type; the condition that a drug is
expelled or destroyed. intended to treat. The condition or symptoms
immunoglobulin A protein produced a particular drug is used to treat are deter-
by plasma cells that fights infection or mined either by evidence of positive effect or
takes part in various immune responses. knowledge of the cause of the disease.
Immunoglobulins bind with other molecules infusion Introducing a solution into the
with a high degree of specificity; divided bloodstream or another solution; also refers
into five classes (IgM, IgG, IgA, IgD, and to the solution itself, such as a drug formula-
IgE) on the basis of structure and biological tion, when infused.
activity. intron Noncoding genetic information
immunohistochemistry The staining removed from pre-RNA in the formation of
of histology preparations using chromagen mRNA in eukaryotes.
linked antibodies to specifically stain for inoculate To introduce cells into a
specific proteins in a histology section/slide. culture medium; also to introduce material
impurity A foreign agent or material either to sensitize patients (as in vaccination).
introduced as part of processing (such as buf- inoculum Material (usually cells) used to
fers or salts added during chromatography) or inoculate.
intrinsic to the nature of bioprocessing (such intact mass analysis A characteriza-
as product variants and cellular debris). tion technique using mass spectrometry
in silico Studies done in the computer. that provides a mass measurement and an
Modeling a protein in silico refers to provid- estimate of the overall heterogeneity of a
ing an integrated, computerized view of the protein.

A Guide to the Biopharmaceutical Lexicon February 2012 33


[ BIOTERMINOLOGY ]

intellectual property (IP) Any and all isoelectric focusing An analytical


patent applications or patents, or trade se- technique that uses electrophoresis in a pH
crets that make up the proprietary informa- gradient (for example 4 to 10) to deter-
tion of a company. mine the isoelectric point (see also pI) of a
interferon A type of cytokine glycopro- polypeptide. May be performed in a gel, in a
tein made by animal cells to inhibit virus liquid, or in a capillary tube (cIEF).
reproduction to fight infection. Interferons isoform A specific and distinct
also affect growth and development (differ- structure or form of a biological molecule
entiation) in certain normal and tumor cells. among a family of biological molecules
interleukins Cytokines produced by with very similar structures and compa-
lymphocytes or macrophages that modulate rable, but not necessarily equal, action for
the immune response. the same product.
intermediates Substances formed in isolation chambers Laboratory cham-
the middle stages of a series of processing bers designed to protect workers from dan-
steps; stepping stones between a parent gerous chemicals, organisms, or substances
substance and a final product. they are working with (or the reverse);
ion mobility separation (IMS) A tech- includes hooded workstations, isolators, and
nology that differentiates ions based on a clean rooms, for example.
combination of factors: their size, shape and isomerization Changes that create
charge, as well as their mass. IMS provides isomers (molecules with the same chemical
an orthogonal dimension of separation. make-up but a different structure), which
Coupling of ion mobility measurements and alters the activity of most proteins.
separations with tandem mass spectrometry isopycnic Describes molecules that have
can be applied to the gas-phase structures of the same buoyant density in ultracentrifu-
biomolecules. (See also HDMS) gation. Molecules of differing densities form
iontophoretic delivery Introduction of different regions in equilibrium within a
drugs through intact skin using the transfer density gradient medium.
of ions by applying a direct electric current. isotonic Having the same osmotic pres-
IQ Installation Qualification; documented sure as blood serum, thus easily mixed with
verification that all aspects of a facility, the blood.
utility, or equipment that can affect product isotope An alternative form of an ele-
quality adhere to approved specifications ment having a different number of neutrons
and are correctly installed. in its atomic nucleus.
IRB Institutional review board; a commit-
tee or other group (composed of medical,
scientific, and nonscientific members) that is KL
responsible for protecting the rights, safety, kDa kiloDalton; a thousand Daltons.
and well-being of human subjects participat- knockout Gene targeting; for instance,
ing in clinical trials. a knockout mouse is one in which a single

34 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

gene is inactivated (knocked out), leaving Leachables are potential extractables, and
other genes unaffected; provides the best may be evaluated by USP standard tests.
way to delineate the function of a gene. lead 1. A molecule that modulates the
LAL assay Limulus amebocyte lysate activity of a receptor or other target protein.
assay; detects pyrogenic endotoxins using a Successful lead compounds become candi-
reagent that was discovered in the blood of dates for drug development. 2. Pb, a toxic
Limulus horseshoe crabs. heavy metal.
laminar flow clean air device A clean legacy system Old hardware and
bench, clean workstation, and wall or ceiling software applications in which a company
modules or other devices that incorporate a has already invested considerable time
filter and motor blower for supplying clean and money, and which is no longer state-
air in one direction for a controlled work of-the-art or compliant with regulatory
space; more correctly referred to as unidi- requirements.
rectional airflow, which is air flow having Leu Leucine; one of more than 20 natu-
generally parallel streams operating in a rally occurring amino acids.
single direction and with uniform velocity ligands Molecules or ions that chemically
over its cross section. bind to certain other molecules or ions. In
LC/MS systems Liquid chromatography/ a binding action, usually the smaller of the
mass spectrometry systems; laboratory two molecules is considered the ligand.
instruments that combine two popular ana- ligase An enzyme that causes molecular
lytical methods into one piece of equipment. fragments (such as DNA, RNA, or peptides) to
LC/IMS/MS systems Liquid chromatog- link together; DNA ligase is used with restric-
raphy/ion mobility/mass spectrometry sys- tion enzymes to create recombinant DNA.
tems; laboratory instruments that combine light-scattering analysis Analytical
three popular analytical methods into one method that gives information about the size
piece of equipment. and shape of molecules based on how they
LC/MS/MS Liquid chromatography disperse ultraviolet and visible light.
with tandem mass spectrometry detec- LIMS Laboratory information manage-
tion; a highly selective method using an ment system; computers and software that
atmospheric-pressure ionization tandem handle all the data produced by laboratory
mass spectrometer to measure the differ- research and analytical methods.
ence in the mass-to-charge ratio of ionized liquid chromatography Analytical
molecules and fragments. method used to separate mixtures of sub-
leachable Chemical entity that has the stances based on the differential distribution
potential to be extracted from a container of the substances between a stationary
or closure when exposed to certain condi- phase (material such as silica gel or silicic
tions of solutions. Examples of common acid, usually contained in a column, tube,
leachables seen in pharmaceuticals include or capillary) and a liquid mobile phase (a
plasticizers, metals, accelerating agents. medium that carries the sample through

A Guide to the Biopharmaceutical Lexicon February 2012 35


[ BIOTERMINOLOGY ]

the stationary phase). This very effective cellular membrane of cells by chemical,
technique can separate substances that are enzymatic, or mechanical means. A solution
nearly identical. containing the contents of lysed cells is
liquid fractionation Any of several called a lysate.
precipitation or phase-separation methods lysosomes Cell organelles containing
used to determine the molecular weight dis- enzymes, responsible for degrading proteins
tribution of polymers, based on the tendency and other materials ingested by the cell.
of polymers of high molecular weight to be
less soluble than those of low weight.
lot A GMP-defined word used to refer to M
an entire batch of product. MAb Monoclonal antibody; a highly
lot release testing Samples from each specific, purified antibody that recognizes
drug lot (batch) manufactured for clinical only a single epitope.
trials or (later on) for sale are tested to prove MAC Mammalian artificial chromosome;
that the batch meets specifications for con- a vector used to clone DNA fragments larger
tent and purity before it is released for use. than 100,000 base-pairs long. As sug-
luciferase In luminiscent organisms gested by the name, MACs are constructed
(fireflies, some bacteria, and certain from mammalian cell DNA.
marine organisms), luciferase is an enzyme macrokinetics Movement of whole cells
that acts on species-specific light-emitting and their media within a bioreactor.
substances known as luciferins. Chemi- macromolecules Very large molecules
luminescent assay systems using firefly (proteins, carbohydrates, nucleic acids),
luciferinluciferase have detected small often formed by two or more identi-
amounts of ATP, the energy-storage com- cal molecules in a chain configuration
pound of a cell. Such systems may serve (polymers).
as alternatives to radioimmunoassays and MALDI-TOF Matrix-assisted laser
fluorescence methods. desorption ionizationtime of flight; mass
lymphocytes White blood cells that spectrometry technique for determin-
produce antibodies. ing molecular weight. Electrons become
lyophilization Freeze-drying; a proce- excited after laser irradiation, transfer-
dure by which a liquid solution is frozen to a ring energy into the mixture and causing
glassy state (primary drying), then slightly molecules and ions to be ejected from its
heated to remove the unfrozen water by surface. Commonly used in proteomic and
sublimation. peptide analyses.
Lys Lysine; one of more than 20 natu- mannitol A sugar alcohol (found
rally occurring amino acids. naturally in many plants, algae, and fungi)
lysed-cell slurry A mixture of the debris that is obtained by reducing mannose and
formed by disintegrating or breaking cells. used as a pharmaceutical excipient and in
lysis Disruption or breaking of the diagnostic tests of kidney function.

36 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

mannose A sugar (an aldohexose) often use. (See working cell bank)
used as an excipient in drug formulations. media Plural form of medium, a (usually
mass spectrometry Mass spectrometry sterile) preparation made for the growth,
(MS) is an analytical technique that mea- storage, maintenance, or transport of micro-
sures the mass-to-charge ratio of charged organisms or other cells.
particles. It is used for determining masses Met Methionine; one of more than 20
of particles, for determining the elemental naturally occurring amino acids.
composition of a sample or molecule, and metered dose inhaler (MDI) A device
for elucidating the chemical structures used to deliver a fixed volume or dose of an
of molecules, such as peptides and other aerosol form of an active drug substance to
chemical compounds. The MS principle the lungs and/or bronchi.
consists of ionizing chemical compounds metabolism Drug metabolism is the
to generate charged molecules or molecule biochemical modification of pharmaceutical
fragments and measuring their mass-to- substances by living organisms, usually
charge ratios. through specialized enzymatic systems. This
master batch record The template that is a form of xenobiotic metabolism. Drug
describes the step by step procedures to be metabolism often converts lipophilic chemi-
followed during manufacturing, with spaces cal compounds into more readily excreted
to record actual data. The master batch polar products. Its rate is an important
record is uniquely identified, under change determinant of the duration and intensity of
control, pre-approved by quality assurance, the pharmacological action of drugs.
and used to generate each individual batch metabolites Chemical products of me-
record that is issued when a given batch is to tabolism, the chemical process of life.
be manufactured. micelle A spherical arrangement (bub-
master cell banks A master cell bank is ble) formed by a group of lipid molecules
prepared by culturing a homogeneous popu- in an aqueous environment; hydrophobic
lation of cells, such as an established, cloned ends of the molecules are turned inward and
cell line, under defined conditions and then hydrophilic ends are turned outward. A mo-
distributed into containers in a single opera- lecular aggregate that constitutes a colloidal
tion, processed together to ensure uniformity, particle (a substance consisting of particles
and stored to ensure stability. Each vial is dispersed throughout another substance with
presumed to have comparable properties, particles too small for resolution with an
and thus the bank may be characterized by ordinary light microscope, but that can pass
testing a representative number of individual through a semipermeable membrane).
vials. Cell cultures derived from the master microassays Assays usually run on very
cell bank are used to prepare working cell small samples, often using microplates,
banks for manufacturing of a biopharmaceu- and often automated. Microplates can have
tical. Both master and working cell banks are room for 96, 384, or even 1,536 tiny
extensively tested and characterized before samples. Microassays measure small quanti-

A Guide to the Biopharmaceutical Lexicon February 2012 37


[ BIOTERMINOLOGY ]

ties of components even when the sample from only some of the molecules. The
size is large. purified product is then a mixture of a
microbial fermentation Processes protein with the native sequence and a
involving the use of microorganisms, such protein with the native sequence plus the
as E. coli, to produce a protein or other extra amino acid.
substance. microinjection Manually using tiny
microbial testing Analytical methods needles to inject microscopic material (such
required by regulations to ensure steril- as DNA) directly into cells or cell nuclei;
ity and to measure bioburden or identify video screens provide a magnified view.
microorganisms in controlled, classified micron See micrometer. The preferred
environments. term is micrometer.
microbiology The study of microscopic micrometer One millionth of a meters
life such as bacteria, viruses, yeast, and length. Abbreviated as m.
protozoa. microorganism A microbe; a free-living
microcarrier A microscopic particle (of- organism too small to be seen by the
ten a 200 m polymer bead) that supports naked eye.
cell attachment and growth in suspension microspheres Tiny polymer spheres
culture; alternative to microencapsulation. (usually biodegradable) measured in
Cells anchor into tiny pores on the beads for micrometers.
protection. miRNA A single-stranded RNA molecule
microencapsulation In cell culture, trap- of about 21 to 23 nucleotides in length,
ping cells inside a thin protective membrane which regulates gene expression.
to provide anchorage and protect them from mitochondria Animal-cell organelles
harsh conditions. Microspheres are often that reproduce using their own DNA. They
biodegradable. metabolize nutrients to provide the cell with
microfiltration A method of sterile energy and are believed to have once been
filtration, clarification, or cell harvest- symbiotic bacteria. Chloroplasts are their
ing that removes particles in the 0.1 to plant-cell equivalents.
10.0 m range. MOBCAL Software that calculates mobili-
microheterogeneity In biopharma- ties. MOBCAL is an open-source software
ceuticals, usually small differences in and is command-line driven (www.indiana.
the amino acid sequence or structure edu/nano/software.html).
of a polypeptide chain. For example, to moiety One of the portions into which
produce a recombinant protein in E. coli, something is divided; a component, part,
a Met must be added to one end of the or fraction. In chemistry, a specific section
protein sequence to act as a signal that of a molecule, usually complex, that has a
initiates protein synthesis. In most cases, characteristic chemical effect or property.
that Met is removed once the protein is mole The amount of a substance that
made. Sometimes the Met is removed contains the same number of elements (such

38 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

as atoms, molecules, or ions) as there are analysis to obtain both MS and MS/MS data.
atoms of carbon in 12 grams of carbon-12; Data acquired in MSEE mode can be mined at
one mole contains Avogadros number of a later date for different information.
molecules (6.02 x 1023). multicellular Referring to organisms
monomer A simple molecule that may composed of more than one celloften bil-
combine with others to form polymers. lions of themarranged in various organs,
monosaccharide (see carbohydrate) tissues, and systems.
mRNA Messenger RNA; which serves as multimer Any small polymer; in biophar-
a template for protein synthesis. It is made maceuticals, usually a protein made up of
as a complement to a DNA sequence and more than one polypeptide chain.
then transported from the cell nucleus to the multimer formation Association of pep-
ribosomes. tide or protein molecules to produce dimers
MSDS Material safety data sheets; docu- (two linked identical molecules), trimers
mentation (including data describing physical (three linked identical molecules), and so on
characteristics, toxicity, health effects, first depending on how many identical molecules
aid, reactivity, storage, disposal, protective link up together
equipment, and spill/leak procedures) that mutagen An agent (chemicals, radiation)
provides workers and emergency personnel that reacts with DNA to produce mutations.
with the proper procedures for handling or mutagenicity The degree to which a
working with a particular substance. substance can cause a change in an organ-
MSEE The simultaneous acquisition of ex- isms DNA.
act mass data using alternating collision cell mutation A permanent change in DNA
energies. This technique is unique to Waters sequence or chromosomal structure.
mass spectrometers, which can perform this MW molecular weight; refers to the mass
simultaneous data capture at UPLC speed of a molecule, usually stated in Daltons.
(see also UPLC). The MSEE approach, when mycoplasma Parasitic microorganisms
used to acquire precursor and product ion that infect mammalian cells, possessing
information, has the additional benefits of some characteristics of both bacteria and
obtaining both types of data in one analyti- viruses. Prokaryotic microorganisms, fam-
cal run. Both the precursor and product ion ily Mycoplasmataceae, with no cell walls
data are acquired in accurate mass mode (therefore resistant to many antibiotics) and
so that elemental composition information needing sterols for maintenance and growth.
can be generated from both sets of data. Potential contaminants of mammalian cell
Another advantage of MSEE is that neutral cultures, they may grow attached or close
loss information from a comparison of the to cell surfaces in the cytoplasm, subtly
two alternating collision energy scans can be altering properties of the cells, but escaping
obtained, eliminating the need for any further detection unless specifically monitored. In
experimentation. The mode of operation also cell culture of biopharmaceuticals, each lot
removes the need for time-consuming re- must be tested at the end of cell culture for

A Guide to the Biopharmaceutical Lexicon February 2012 39


[ BIOTERMINOLOGY ]

mycoplasma contamination; a confirmed uses radiation in the near-infrared range


positive results in batch rejection. to provide rapid, nondestructive analysis
myeloma Lymphocytic cancer; a malig- of materials.
nancy found in bone marrow. NIST National Institutes of Standards and
Technology; a federal agency that develops

N and certifies standard reference materials


for use in various US industry applications
native The natural state; in a biopharma- NMR spectroscopy Nuclear magnetic
ceutical context, it usually refers to a mol- resonance spectroscopy; an analytical
ecules normal three-dimensional structure method that generates a spectrum (based
under optimal conditions. on the electromagnetic environment
NDA New Drug Application; CDERs surrounding the nucleus of each atom in
equivalent of the BLA. It is used for small- a molecule) that serves as the chemical
molecules and some biopharmaceuticals signature of each molecule and aids in
(such as hormones and small peptides), structure determination.
which are regulated by CDER rather than nonconformity A deficiency in a
CBER. characteristic, product specification, process
nebulizer A device, pressurized by an parameter, record, or procedure that renders
oxygen or nitrogen tank, for the purpose the quality of a product unacceptable,
of converting a liquid (such as a medicinal indeterminate, or not according to specified
formulation) into a fine mist (to be inhaled, requirements. [From FDAQSG]
for example). norleucine An amino acid, not produced
nick translation A technique used to by mammalian cells, but may be produced
introduce radioactively and nonradioactively by many bacteria, especially under condi-
labeled nucleotides into DNA; the new tions of nutrient-poor media. NorLeu may be
nucleotide is added at the position where substituted for Leu when a mammalian protein
the original nucleotide was excised; nick is expressed in bacterial cells, creating new
translation can be used for a number of product variants that may be of safety concern.
hybridization techniques, such as gel blots N-terminal Amino-terminal or amine
and colony plaque lifts. terminus; the amine terminus of a protein
NIH National Institutes of Health; the chain (with a free a-amino group).
US government agency that conducts and nucleic acids DNA or RNA: chainlike
supports medical research and dissemina- molecules composed of nucleotides.
tion of information. One of eight agencies nucleosides Glycosylamines consisting
in Public Health Services, which is in turn of a nucleobase bound to a ribose or deoxy-
part of the US Department of Health and ribose sugar. The most prevalent examples
Human Services. of nucleosides are adenosine, cytidine,
NIR spectroscopy Near-infrared spec- guanosine, thymidine, and uridine.
troscopy; a bioanalytical technique that nucleotides Molecules composed of a

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[ BIOTERMINOLOGY ]

nitrogen-rich base, phosphoric acid, and a to laboratory error, operator error, or process
sugar. The bases can be adenine (A), cyto- error; and a judgment made whether the
sine (C), guanine (G), thymine (T), or uracil result itself is valid (accurate estimate of the
(U). These molecules comprise the basic true value of the analyte) or invalid. Usually,
structural units of RNA and DNA. confirming an OOS result as valid results in
nucleus The largest organelle, a affected lot(s) of product being rejected.
membrane-bounded compartment found in OOT Out of tolerance; 1. refers to
eukaryotes that contains most of the cells equipment or instrument which, when
genetic material and a nucleolus that builds its calibration is checked, is outside of a
ribosomes. defined range and requires adjustment or
repair. 2. Out of trend; a test result that is

O unexpected or outside of its historical or


statistical trends but within specifications;
oligomer A short polymer consisting of and must be investigated as a type of
a few monomers, typically refers to small exception. The investigation is very similar
nucleotide polymer. to an OOS investigation, with the difference
oligonucleotide A short nucleotide that product disposition may not be affected
polymer, typically with 30 or fewer bases. by a confirmed out of trend result.
oligosaccharide (see carbohydrate) operon A group of functionally related,
Omega () The value of Omega is adjacent genes found in prokaryotes that
square angstroms (2). Omega can be cal- operate as a unit to synthesize functionally
culated theoretically for any ionic structure related proteins (enzymes). An operon group
based a three-dimensional structure. Histori- includes an operator region, a regulator
cally, a physical model of the molecule was gene, and structural genes equivalent to the
constructed and mounted between a light number of enzymes in the system.
source and a screen. The area of the shadow optimization Determining and imple-
was measured for many orientations and menting process operation at the best pos-
then an average calculated. The measure- sible and most affordable efficiency.
ment of Omega provides a mechanism for OQ Operational Qualification; document-
comparison of different (ionic) species for ed verification that all aspects of a facility,
this attribute. utility or equipment that can affect product
oncogene A gene that, when ex- quality operate to Intended throughout all
pressed, can lead cells to become cancer- anticipated ranges.
ous, by removing the normal constraints organelle A structurally discrete compo-
on their growth. nent that performs a certain function inside
OOS Out-of-specifications result; a result a eukaryotic cell.
that is outside the range of an approved organic In chemistry, any molecule
specification. An OOS result must be containing carbon atoms is considered an or-
investigated to determine whether it is due ganic molecule (from the Greek for work).

A Guide to the Biopharmaceutical Lexicon February 2012 41


[ BIOTERMINOLOGY ]

membrane under the influence of an osmotic


gradient. Osmotic pressure is the pressure
that must be applied to a solution to prevent
osmosis. Osmotic shock is a rapid change in
osmotic pressure on a cell or virus, usually
causing it to discharge its contents.
outsourcing Having research, laboratory
testing, clinical trials, or manufacturing
done by another firm, usually called the
contract organization. (See sponsor; quality
agreement)
overflow The liquid portion of a broth
after centrifugation when solid particulates
Peptide mapping provides detailed struc- have settled out; describes the part of the
tural information for a protein; it is a chal-
lenging application because of the number centrifuge apparatus that holds the liquid
of peaks that must be baseline-resolved. separate from the solids (the underflow).
The Waters ACQUITY UPLC H-Class Bio oxidation Chemical reaction in which a
System, with Peptide Separation Technol-
ogy Columns, provides maximum LC reso- compound or atom loses valence electrons;
lution and sensitivity for more condence due to reaction with an oxidizing agent
in protein characterization studies.
(e.g., oxygen, peroxides, metal ions, or oth-
Organic chemistry is the chemistry of life ers). Many proteins are prone to oxidation
because carbon interacts in myriad ways on exposure to air (such as oxidation of the
with a large number of other elements to Met amino acid into methionine sulfide or
form complex molecules (RNA, DNA, amino sulfone). (See also redox)
acids, proteins, and so on) that perform the
intricate actions that make life work.
organism A single, autonomous living P
thing. Bacteria and yeasts are organisms; PA projection approximation; an ion is
mammalian and insect cells used in culture modeled by a collection of overlapping hard
are not. spheres with radii equal to hard sphere colli-
orphan drug A US product that treats a rare sion distances. The orientationally averaged
disease affecting fewer than 200,000 people. geometric cross section is determined by
orthogonal At right angles or differing averaging the geometric cross section over
completely. Sometimes used to mean occur- all possible collision geometries.
ring stepwise rather than simultaneously. PAI Preapproval inspection; an FDA facil-
osmolarity The concentration of osmoti- ity inspection performed in response to a
cally active particles in a solution (expressed biopharmaceutical companys filing an NDA.
in osmoles of solute per liter of solution). (See prelicense inspection)
Osmosis is flow through a semipermeable parenteral delivery Drug delivery by

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[ BIOTERMINOLOGY ]

injection; subcutaneous, intra-muscular, and elution fraction). The sharp rise in the line
intravenous delivery are most common. Drug graph of a chromatogram that represents
must be sterile. this phenomenon.
particle filtration Particle filtration is PEG Polyethylene glycol; a polymer
used to filter macro particles, which are vis- that usually consists of a size distribution
ible to the naked eye and range in size from of various molecular weight compounds.
50 m to 1000 m. Examples of particles Physical and chemical properties vary with
in this size range include beach sand, the molecular weight (liquid to solid, viscos-
granular activated carbon, human hair, mist, ity, etc.). PEGs are used as surfactants in
pollen, milled flour, and precipitates formed industry (for foods, cosmetics, and pharma-
during bioprocessing. ceuticals); and in biomedicine as dispersing
passage number When cells are cul- agents, solvents, ointment and suppository
tured, the passage number is a theoreti- bases, vehicles, and excipients.
cal number of cell generations, or how PEGylation Covalent attachment
many times the cells have been pas- of polyethylene glycol molecule(s) to
saged in vitro. a protein molecule via selected amino
PAS Pre-approval supplement; a regula- acid side groups, for example free amino
tory submission to FDA used for biologics or sulfhydryl groups. May be done to
and biopharmaceuticals when major changes decrease toxicity or improve its solubility
to the process, facility, or quality control and circulating half-life in the body.
system are desired. The sponsor must wait peptide bioanalysis The use of analyti-
for full FDA review and approval before cal techniques to quantitatively measure
any product manufactured may be placed peptide drugs and their metabolites in
in distribution. Often, a PAS or a CBE-30 biological systems. Formerly performed
may be part of a comparability protocol, and using ligand-binding assays such as radioim-
the type of submission required for a given munoassay and ELISAs, LC/MS/MS is now
package of changes is negotiated with FDA being applied to peptide bioanalysis for its
by RA personnel. higher accuracy levels. A successful, highly
PAT See process analytical technology. sensitive method for the analysis of peptides
PCR Polymerase chain reaction; a process relies upon a combination of high-perfor-
that exponentially amplifies (reproduces) mance chromatography, mass spectrometry,
a short piece of DNA having a specific and sample preparation.
nucleotide sequence, making possible many peptide bond The carbon-nitrogen
research and clinical applications involving covalent bond (link) between an amino
that DNA (used extensively in forensics). PCR group of one amino acid and a carboxyl
may be qualitative or quantitative (qPCR). group of another, formed by removing water
peak An individual component of a and resulting in the group RCO-NH. This
mixture that is washed out of the chro- linkage does not allow free rotation, and it
matography column during elution (the is the important bond that connects amino

A Guide to the Biopharmaceutical Lexicon February 2012 43


[ BIOTERMINOLOGY ]

acid monomers to form the polymer known identify and describe the critical quality at-
as a polypeptide. tributes and critical process parameters that
peptide mapping Bioanalytical method influence product quality and performance.
in which proteins are selectively cleaved by pharmacodynamics Study of the reac-
enzymes to create a characteristic pattern tions between drugs and living structures,
of peptides that is elucidated through chro- including the processes of bodily re-
matographic separations and spectroscopic sponses to pharmacological, biochemical,
or spectrometric detection. physiological, and therapeutic effects. A
peptides Short polymers formed from PD study seeks to determine where a drug
the linking, in a defined order, of amino ac- penetrates in the body and by means of
ids. The link between one amino acid residue what mechanisms.
and the next is known as an amide bond or a pharmacokinetics Sometimes abbrevi-
peptide bond. ated as PK, (from Ancient Greek pharmakon
perfusion Sometimes perfusion propaga- drug and kinetikos to do with motion;
tion; a cell culture or fermentation process see chemical kinetics) is a branch of phar-
commonly used in antibody production, in macology dedicated to the determination of
which high concentrations of mammalian the fate of substances administered exter-
cells inside a chamber have fresh growth nally to a living organism. The substances
media continually circulated around them for of interest include pharmaceutical agents,
continuous addition of nutrients and removal hormones, nutrients, and toxins. (See also
of waste products. ADME.)
permeate Also called filtrate, the part of Phe Phenylalanine; one of more than 20
a mixture that passes through a filter. naturally occurring amino acids.
pH Power of hydrogen or the log of the phenotype The observable characteristic
concentration of H+ ion in a solution. Mea- that results from the action of an organisms
surement of the relative alkalinity or acidity of genes. Phenotype varies depending on which
a solution. Pure water is pH neutral (7), acidic In pharmaceutical development, analysts
solutions have pH values between 0 and 7, generate information-rich and reliable an-
alytical methods to support IND and NDA
and alkaline or basic solutions have pH values submissions for innovative medicines.
between 7 and 14. Often a critical control
parameter in biopharmaceutical processes.
phage A virus-like parasite that infects
bacteria; also bacteriophage.
pharmaceutical development Col-
lected information from development stud-
ies conducted to establish that the dosage
form, formulation, manufacturing process,
and quality attributes are appropriate for the
product. The development process should

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[ BIOTERMINOLOGY ]

alleles of each gene are present. and self-replicating and found (naturally in
phosphoramidite or nucleoside phos- bacteria and some yeasts) in the cytoplasm
phoramidites The individual base building of cells. They can be used as vectors for
blocks that are used to synthesize short introducing up to 10,000 base-pairs of
nucleic acid chains also known as oligo- foreign DNA into recipient cells.
nucleotides. polar solvent A solvent for molecules
phosphorylation Addition of a phosphate that have permanent electric dipoles.
(PO4) group to a molecule, usually enzymati- polishing The final purification step(s) in
cally done by transferring a phosphate group a biopharmaceutical manufacturing process,
from ATP (adenosine triphosphate). usually involving an affinity or other refined
physical state The form that matter chromatography method. Often this step
takes, whether solid, liquid, gas, or plasma. uses the most expensive technique in the
pI Isoelectric point; the pH at which a process because it handles the smallest
substance has no net charge, above which a amount of material.
substance acts as a base and below which polyacrylamide A high molecular-
it acts as an acid. A solution of proteins or weight polymer of acrylamide (a neurotoxin)
amino acids has its minimum conductivity used as a support and separations matrix in
and viscosity at the isoelectric point. electrophoresis and gel chromatography.
pichia pastoris An alternative yeast polymer A large molecule formed by the
species proposed as a recombinant expres- combination of at least five (and sometimes
sion system. It performs post-translational as many as 1,000) identical smaller mol-
modifications that are more similar to human ecules (monomers).
protein modifications than those performed polymerase An enzyme that catalyzes
by other yeasts used in fermentation. the production of nucleic acid molecules.
pilot plant A medium-scale biopro- polymerize To undergo or subject to
cessing facility used as an intermediate in polymerization, a chemical reaction in which
scaling up processes from the laboratory to two or more molecules combine to form
commercial production. larger molecules that contain repeating
placebo A fake treatment (usually the structural units.
same formulation used for the real product, polymorphism A single mutation in a
but without the active ingredient) adminis- gene at one nucleotide locus that potentially
tered to the control group in a controlled changes gene expression with a modified
clinical trial so that the specific and nonspe- protein that may possess different proper-
cific effects of the experimental treatment ties, for example, the activity of an enzyme
can be distinguished. The experimental with a drug.
treatment must produce better results than polysaccharide A kind of complex
the placebo to be considered effective. carbohydrate (macromolecule composed
plasmid Hereditary material that is not of long chains of simple sugars). Several
part of a chromosome. Plasmids are circular polysaccharides from microorganisms have

A Guide to the Biopharmaceutical Lexicon February 2012 45


[ BIOTERMINOLOGY ]

important commercial uses.


polysorbate 80 A hydrophilic surfactant
commonly used as a pharmaceutical excipi-
ent, among other things.
polysorbates Complex mixtures of
polyoxyethylene ethers used as emulsifiers
or dispersing agents in pharmaceuticals.
polyvinyl A polymer prepared from Laboratories rely on the high purity
polyvinyl acetates by replacement of the and recovery achieved with preparative
chromatography columns.
acetate groups with hydroxyl groups. It is
used as a pharmaceutic aid (a substance protein processing is done by the Golgi
with little or no therapeutic value that is bodies after proteins have been construct-
necessary in the manufacture, compounding, ed by ribosomes.
or storage of pharmaceutical preparations or potency The measure of the biologi-
drug dosage forms). Polyvinyls are used as cal activity using a suitably quantitative
solvents, diluting agents, suspending agents, biological assay (also call potency assay
and emulsifying agents. or bioassay), based on the attribute of the
polyvinyl alcohol A synthetic polymer product that is linked to the relevant biologi-
used as a fixative and an adhesive and as an cal properties. [From ICH Q6B]
emulsifying agent, thickener, and stabilizer. PQ Performance qualification; Document-
Specimens can remain in PVA without dam- ed verification that all aspects of a facility,
age for long periods of time. utility or equipment perform as intended in
postapproval changes Changes (scale- meeting predetermined acceptance criteria.
up, for example) made to a biopharmaceuti- pre-license inspection An FDA facil-
cal manufacturing process after the drug has ity inspection performed in response to a
been approved for marketing. biopharmaceutical companys filing of a BLA
postmarketing surveillance Phase to confirm claims made in the license ap-
4 clinical trials, which provide additional plication and assess the readiness and cGMP
details about a products safety (while the compliance of the manufacturing plant.
product is on the market) and efficacy and precipitation Process causing a solid to
may be used to evaluate formulations, settle out of solution (as in centrifugation)
dosages, durations of treatment, medicine by the action of gravity or by a chemical
interactions, additional indications, and reaction; a reaction between a soluble
other factors. antibody and a soluble antigen, resulting
post-translational modification (PTM) in the formation of a substance (known as a
After a DNA sequence has been inter- precipitate) that separates, in solid particles,
preted and a protein has been created, it from a liquid.
may be modified by the addition of sugar preformulation An exploratory activity
(glycosylation) or other molecules. This that begins early in biopharmaceutical

46 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

development, involving studies designed called TSEs. (Term originally derived from
to determine the compatibility of initial proteinaceous infectious particle.)
excipients with the active substance for a Pro Proline; an imino acid often grouped
biopharmaceutical; physicochemical and with the 20 naturally occurring amino acids.
bioanalytical investigation in support of process analytical technology (PAT)
promising experimental formulations. A system for designing, analyzing, and
preparative chromatography Chroma- controlling manufacturing through timely
tography methods used in manufacturing measurements (i.e., during processing) of
rather than analytical applications, larger in critical quality and performance attributes of
scale and intended to purify a product; also raw and in-process materials and processes
called process chromatography. Chromato- with the goal of ensuring final product qual-
graphic methods were first used in analytical ity. [From ICH Q8]
laboratories, and only later in the 20th process control 1. The means by which
century were they adapted to industrial a process is monitored and operated, and
separations use. (Contrast with small-scale is designed to maintain critical parameters
analytical chromatography.) within set ranges determined to be safe. 2.
preservative A chemical additive that A consistent process that follows predictable
prevents spoilage by killing or inactivating statistical trends and is monitored using
microorganisms; also stabilizes molecules control charts is said to be in a state of
such as when using antioxidants or sulfhy- statistical control.
dyls to stabilize proteins. (Contrast with bac- process development The step in the
teriostatic agent, which prevents microbes life cycle of a product that starts with
from multiplying but does not kill them). information from research, and deliv-
primary recovery The early steps in ers a scalable process to manufacturing
separation and purification of a biophar- plants that can be validated, operated
maceutical, in which a complex biological under cGMP controls, and be commercially
solution containing the protein of interest is viable. During process development,
concentrated and clarified, usually by means preclinical and clinical trials supplies of
of filtration, centrifugation, or extraction the product are manufactured.
(precipitation); and the protein of interest process knowledge A compilation of all
is isolated from residual debris, cells, and facts about a manufacturing process from
other macromolecular materials. development through full-scale manufacture.
primary structure The amino acid process-related impurities Impurities
sequence of a biomolecule. that are derived from the manufacturing
prion Believed to be the smallest, process. They may be derived from cell
simplest infectious particle consisting of a substrates (e.g., host cell proteins, host cell
hydrophobic protein (no nucleic acid, DNA, or DNA), cell culture (e.g., inducers, antibiotics,
RNA), suggested as a possible model for the or media components), or downstream pro-
causal agent of scrapie and related diseases, cessing (e.g., processing reagents of column

A Guide to the Biopharmaceutical Lexicon February 2012 47


[ BIOTERMINOLOGY ]

leachables). [From ICH Q6B] rable to the desired product and are not
process robustness Ability of a process to considered impurities. [From ICH Q6B]
tolerate variability of materials and changes product specification A list of tests and
of the process and equipment without nega- acceptance criteria (limits) that are used to
tive impact on quality. [From ICH Q8] define the quality of a drug substance or
process understanding Comprehension drug product. The specification is often listed
of process knowledge such that all critical on the Certificate of Analysis along with
sources of variability are identified and results for a specific batch or lot.
explained; variability is managed by the product variant A molecule that is
process; and product quality attributes can related to the product but differs from it
be accurately and reliably predicted over the chemically, such as a degradation product,
design space established for the materials intermediate, or different configuration of
and process. Through process understanding, the protein of interest due to deamidation or
process performance and product attributes other chemical reactions. A product variant
can be explained logically and scientifically is form (charge isoform, n- or c- terminal
as a function of process parameters, inputs, form, eglycoform, etc.) that is considered
and input material attributes. part of the product definition.
product lifecycle All phases in the life prokaryotes Simple organisms, such as
of the product, from the initial development bacteria, with no cell nuclei and only a few
through marketing until the products discon- cell organelles.
tinuation. [From ICH Q9] protease An enzyme that cleaves the
prodrug A modified version or precursor peptide bonds linking amino acids in protein
of a parent compound designed to enhance molecules, classified according to the most
delivery properties and be converted to the prominent functional molecular group (such
parent compound in the body. as serine or cysteine) at the active site; also
product-related impurities Molecu- called proteinase.
lar variants of the desired product (e.g., proteinase K A serine protease (used
precursors, aggregates, certain degrada- in molecular cloning and DNA sequenc-
tion product arising during manufacture ing, nucleic acid research, and protein and
and/or storage) that do not have properties peptide structural analysis) with broad
comparable to those of the desired product specificity toward aliphatic, aromatic, and
with respect to activity, efficacy, and other hydrophobic amino acids, cleaving
safety. [From ICH Q6B] their peptide bonds.
product-related substances Molecular protein conformation The characteristic
variants of the desired product formed three-dimensional shape of a protein, includ-
during manufacture and/or storage that are ing the secondary, tertiary, and quaternary
active and have no deleterious effect on structure of the peptide chain.
the safety and efficacy of the drug product. protein folding A rapid biochemi-
These variants possess properties compa- cal reaction involved in the formation of

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[ BIOTERMINOLOGY ]

proteins. It begins even before a protein proteomics Study of protein function and
has been completely synthesized and structure.
proceeds through discrete intermediates protocols Documentation (submitted to
(primary, secondary, and tertiary struc- FDA or other agency in support of regulatory
tures) before the final structure (quater- filings) that directs the work performed in an
nary structure) is developed. FDA-regulated company. Protocols tell who
protein truncation Shortening a directs which activities, who approves what,
polymeric chain of amino acids; the protein and who is allowed to sign off on materials
truncation test developed by Dutch research- and products, even where to find specific
ers screens proteins to identify abnormally files and documentsall tying together
short molecules that suggest the location of numerous SOPs.
genetic mutations. PTC Points to Consider; PTC documents
protein variants Proteins with the same are not regulations with the force of law, but
amino acid sequences but different folds or are instead guidelines on issues that FDA
different carbohydrate residues. They must believes should be considered by regulated
be separated from the therapeutic proteins. industry. These documents are not definitive
proteins Complex organic macromol- or all-inclusive. In fact, they are presented
ecules whose structures are coded in an as drafts subject to further modification,
organisms DNA. Each is a chain of more and readers are invited to submit com-
than 40 amino acids in peptide linkages ments. They acknowledge that processes
that folds back upon itself in a particular and associated knowledge change with time.
way. Proteins are the principal constituent They suggest and recommend procedures
of all cell protoplasms (the entire contents that manufacturers should consider during
of a live cell). Each protein has a unique, ge- development of new drugs and biologics.
netically defined amino acid sequence that purification A central part of down-
determines its specific shape and function stream processing that takes a crude
(as enzymes, structural elements, hormones, fermentation supernatant or cell homog-
and immunoglobulins, involved in oxygen enate (a chaotic slurry of tissues and cells)
transport, muscle contraction, or electron and isolates the product from it in a fairly
transport, for instance). pure form.
proteolysis Separation (cleavage) of pyrogen Any fever-inducing (pyrogenic)
peptide bonds in proteins by proteases substance; more specifically, a lipopolysac-
(enzymes that recognize and cut specific charide (the major constituents of the cell
peptide bonds) or other means. walls of Gram-negative bacteria). The major
proteolytic Capable of lysing (denatur- endogenous pyrogen in mammals is prob-
ing, or breaking down) proteins. ably interleukin-1, production of which is
proteome The complete listing and stimulated by lipopolysaccharide.
description of all the proteins and their func- pyrogenic endotoxins Components
tions for an organism. of bacteria (such as lipopolysaccharides)

A Guide to the Biopharmaceutical Lexicon February 2012 49


[ BIOTERMINOLOGY ]

that induce a feverish immune response in trometry. It consists of four circular rods,
higher organisms. set perfectly parallel to each other. Ions
are separated in a quadrupole based on

QR the stability of their trajectories in the


oscillating electric fields that are applied
QA Quality assurance; 1. The quality to the rods, thus filtering the sample ions
systems and processes used to control based on their mass-to-charge ratio.
every step of pharmaceutical manufacturing qualification 1. Documenting that
to ensure that the product meets all of its a piece of equipment does what it was
specifications and quality attributes, and designed to do, was installed correctly,
that all steps were done and documented in and continues to operate within specified
compliance with cGMP. 2. The sole work unit parameters over time. 2. A term used
that is empowered to disposition drug prod- during process or analytical development
uct and drug substance (release or reject) to describe the experiments that are done
for use in humans; and that provides and prior to validation of the assay or process,
sustains quality systems such as document that define the critical parameters and
control, corrective and preventive actions, design space. 3. Analytical instruments are
audits and oversight. qualified to ensure fitness for intended use
QC Quality control; 1. the system of test- (USP <1058>). See also DQ, IQ, OQ, PQ.
ing that confirms and measures the quality This term sometimes is used interchange-
of raw materials, process intermediates, ably with validation.
final product, and environmental samples, quality The suitability of either a drug
during ongoing production as well as during substance or drug product for its intended
start-up and validation. 2. The work unit use. This term includes such attributes as
that usually performs testing regulated the identity, strength, and purity (from ICH
under cGMP and evaluates results against Q6A Specifications: Test Procedures and
specifications, action limits, or targets, and Acceptance Criteria for New Drug Sub-
makes technical recommendations to QA. stances and New Drug Products: Chemical
May be in the same department as QA in Substances). [From ICH Q8]
some organizations. Quality by Design (QbD) A term defined
QTof A hybrid mass spectrometer design by the ICH quality guidelines, meaning the
that couples time-of-flight (TOF) instrument use of science, engineering, and statistical
with a quadrupole. This pairing results in a tools, as appropriate, to design quality into a
combination of performance characteristics: process or product, or device; and to mistake-
accurate mass measurement, the ability to proof or design out common errors.
carry out fragmentation experiments, and quality risk management A systematic
high quality quantitation. process for the assessment, control, com-
quadrupole mass analyzer One type munication and review of risks to the quality
of mass analyzers used in mass spec- of the drug (medicinal) product across the

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[ BIOTERMINOLOGY ]

product lifecycle. [From ICH Q9] material from another organism. Genetically
quality system A series of processes altered microorganisms are usually referred
that are linked together and controlled to as recombinant, whereas plants and
centrally to increase assurance of product or animals so modified are called transgenic.
manufacturing process quality. Term used by (See also transgenics)
FDA, ICH, and ISO to define those systems recovery Purifying a molecule of interest
that are created and maintained by QA to from the mix of biological components pro-
support GMP operations. Examples include duced by a biotech manufacturing fermenta-
documentation, facility, equipment, packag- tion or cell culture process.
ing, and labeling. redox Equilibrium reaction of oxida-
quaternary protein structure The tion/reduction, for example, thioldisulfide
defined organization of two or more exchange, a step used during refolding
macromolecules with tertiary structure of recombinant proteins that contain Cys
such as a protein that are held together by residues, in order to form correct pairing
hydrogen bonds and van der Waals and of sulfhydryl groups (SH) and form stable
coulombic forces. disulfide (SS) bonds.
radiolabeled Covalently labeled with a reducing agent A molecule that donates
radioactive isotope or substance. an electron in an oxidation-reduction reac-
R&D Research and development; dis- tion, which is a chemical change in which
covering and developing new products; the one species is oxidized (loses electrons) and
department within a company that does so. another species is reduced (gains electrons).
raw material Term with differing Reducing agents such as active metals
definitions in different documents; com- (sodium, magnesium, aluminum, and zinc)
monly means all materials that are used can be used to take the place of proteins and
to manufacture a drug substance or drug keep them from being oxidized.
product, and regulated by 21 CFR 84. (See regeneration (of a column) The act of
also components, starting materials). stripping and cleaning a chromatographic
reanneal The process of renaturing resin of any bound product or contaminants,
complementary single-stranded DNA mol- then stabilizing the surrounding environ-
ecules to yield duplex molecules. ment in preparation for reuse, usually done
recall Product recall; the act of locating by a sequence of various solvents or buffers.
all units of a given lot of product that have regulatory affairs Drug companies
been placed in the distribution chain for must show that their products consistently
human use and recalling them, for cause. meet standards set by government agen-
Recalls are classified based on a risk assess- cies and that manufacturing stays within
ment. (See also withdrawal) approved boundaries defined in the license
recombinant Refers to DNA (or the pro- application. Regulatory affairs departments
tein resulting from such DNA) that has been document those activities, submit propos-
genetically engineered to contain genetic als, and follow those proposals through

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[ BIOTERMINOLOGY ]

completion or approval. RA provides held back by a filter because of its size,


regulatory strategy, and sets up meetings shape, and/or charge.
with regulatory bodies, and determines when retention time The period of time be-
formal notification or submissions to FDA tween initial application of an elution buffer
and other regulatory bodies are required. and the exit from the column of a particular
RA is also involved during product recalls or sample component.
withdrawals. reversed-phase chromatography An
reproductive toxicology Studies of a elution procedure used in liquid chromatog-
drug substance in certain animal models raphy in which the mobile phase is signifi-
to look for any impact on the test animals cantly more polar than the stationary phase,
reproductive function. e.g., a microporous silica-based material
requirements The explicit or implicit with alkyl chains chemically bonded to its
needs or expectations of the patients or their accessible surface.
surrogates (e.g., healthcare professionals, RIA Radioimmunoassay; a bioanalytical
regulators and legislators); includes not method that uses specific antibodies and ra-
only to statutory, legislative, or regula- diolabeled detector molecules to quantitate
tory requirements, but also such needs and a defined analyte in mixtures. For safety
expectations. [From ICH Q9] considerations, many immunoassays are
residue An amino acid when referred to now performed using dyes or other markers
as part of a polypeptide chain. in lieu of the radioactive label.
resin Any of several solid or semi-solid RNA Ribonucleic acid; the nucleic
inflammable substances, of natural or acid based on ribose (a sugar) and the
synthetic organic origin; usually translucent nucleotides G, A, U, and C. It translates
polymers that do not conduct, that break like the information encoded by DNA into
glass, and that are soluble in ether, alcohol, amino acid sequences the cell uses to
and essential oils but not in water. The word make proteins. Similar to DNA but based
is used generically to describe chromato- on ribose, and with the base uracil (U)
graphic media, particularly polymer beads. in place of thymine (T). Various forms of
resolution A measure of the distin- RNA are found: mRNA (messenger RNA);
guishability of individual elements (the tRNA (transfer RNA); and rRNA (ribosomal
component parts of a mixture, for example). RNA). Most RNA molecules are single-
In chromatography, the quality of separation stranded, although they can form double-
measured in terms of the purity of the result- stranded units.
ing component fractions (higher resolution RNAi RNA interference; a system that
means greater purity). regulates what genes are active and
restriction enzyme A bacterial enzyme how active they are. Two types of RNA
that cuts DNA molecules at discrete base- molecules, microRNA (miRNA) and small
pair locations. interfering RNA (siRNA), are central to
retentate The part of a mixture that is RNA interference.

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risk The combination of the probability severity of that harm. [From ICH Q9]
of occurrence of harm and the severity of risk review Review or monitoring of out-
that harm. [From ICH Q9; see also ISO/IEC put/results of the risk management process
Guide 51] considering (if appropriate) new knowledge
risk acceptance The decision to accept and experience about the risk. [From ICH Q9]
risk. [From ICH Q9; see also ISO Guide 73] robust Strongly formed or constructed,
risk analysis The estimation of the sturdy; a product or process that doesnt
risk associated with the identified hazards. break easily or remains stable and (for a
[From ICH Q9] process) reproducible despite physical and
risk assessment A systematic process chemical stress or varying conditions.
of organizing information to support a risk roller bottle A container with large
decision to be made within a risk manage- growth surfaces in which adherent cells
ment process. It consists of the identification can be grown in a confluent monolayer.
of hazards and the analysis and evaluation The bottles are rotated or agitated to keep
of risks associated with exposure to those cells in contact with growth media, but
hazards. [From ICH Q9] they require extensive handling, labor, and
risk communication The sharing of media. In large-scale vaccine produc-
information about risk and risk manage- tion, roller bottles have been replaced by
ment between the decision maker and other microcarrier culture systems that offer
stakeholders. [From ICH Q9]. the advantage of scale-up, minimizing
risk control Actions implementing risk contamination.
management decisions. [From ICH Q9; see R subgroup (or side chain) The group
also ISO Guide 73] of atoms that differs among different
risk evaluation The comparison of amino acid molecules and thus deter-
the estimated risk to given risk criteria mines their diverse chemical properties;
using a quantitative or qualitative scale for example, the R subgroup on a Gly
to determine the significance of the risk. molecule is simply a hydrogen atom, on an
[From ICH Q9] Ala it is a methyl complex (a carbon atom
risk identification The systematic use of and three hydrogens), and on Glu it is a
information to identify potential sources of combination of carbon, oxygen, nitrogen,
harm (hazards) referring to the risk question and hydrogen atoms.
or problem description. [From ICH Q9]
risk management The systematic ap-
plication of quality management policies, S
procedures, and practices to the tasks of Saccharomyces cerevisiae Brewers
assessing, controlling, communicating, and yeast, familiar to cooks as the yeast used
reviewing risk. [From ICH Q9] to leaven bread, was the first and is still
risk reduction Actions taken to lessen the most widely used yeast species in
the probability of occurrence of harm and the biotechnology. Certain strains are used in

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[ BIOTERMINOLOGY ]

the manufacture of alcoholic beverages and aiding in their separation. Analytical separa-
fermented foodsand also for expression tion technique, often used to characterize
of genes. Biologically active interferons, proteins or mixtures, that uses a charged gel
for example, have been produced in it and it environment through which molecules of
can be used in the manufacture of biologics. varying sizes and electric charges migrate
Commonly abbreviated: S. cerevisiae. from one pole to the other. Unlike gel-filtra-
scale-down To model a biopharmaceuti- tion chromatography, larger molecules move
cal manufacturing process (or section of that more slowly than smaller molecules because
process) at the laboratory scale, usually for migration rate is not dependent on diffusion
validation or other study purposes. Scale- into and out of particles.
down requires holding the critical param- SEC Size-exclusion chromatography, gel-
eters constant, and may be confounded by filtration or gel-permeation chromatography.
differences in equipment dead volumes, An analytical method that uses porous
performance, or materials of construction. particles to separate molecules of different
scale-up To transfer a biopharmaceutical sizes. Molecules that are smaller than the
manufacturing process from the laboratory pore size can enter the particles and there-
scale to a manufacturing scale while holding fore have a longer path and longer transit
critical parameters constant. time than larger molecules that cannot enter
Schizosaccharomyces pombe The sec- the particles. SEC can separate biological
ond most commonly used yeast species in molecules and help scientists determine the
biotechnology, originally used in east Africa molecular weights and molecular weight
to brew millet beer, but which is typically distributions of polymers.
unsuitable for other types of fermentation SNP Single-nucleotide polymorphism (See
because of the large amount of sulfurous DNA fingerprinting).
compounds it emits. secondary structure In proteins,
SDMS Scientific Data Management the folding, twisting, coiled, sometimes
System; an automated, electronic repository spring-like chain that results when hydrogen
that stores and manages all types of scien- bonds form between the adjacent parts of a
tific data to a centralized database, offering molecule, as in an alpha helix or beta sheet.
integration with a multitude of research seed stock The initial inoculum or the
applications. cells placed in growth medium from which
SDS Sodium dodecyl sulfate; an ionic other cells will grow.
detergent that binds to and denatures sequence The precise order of bases in a
proteins, and binds in rough proportion to nucleic acid or amino acids in a protein.
the size of the protein; used to aid analyti- Ser Serine; one of more than 20 natu-
cal separations. rally occurring amino acids.
SDS-PAGE Sodium dodecyl sulfate- serum The watery portion of an animal
polyacrylamide gel electrophoresis; the SDS or plant fluid (such as blood) remaining after
detergent denatures and binds to proteins, coagulation.

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shear Tearing force (to cells), such as that sodium hydroxide A highly caustic,
caused by blending or stirring. alkaline chemical (NaOH) used to neutralize
shelf life The period of time during which acids and destroy soft body tissues (with
a drug can be stored without decreasing in potassium hydroxide, the most widely used
quality, safety, or efficacy. caustic agent in industry).
sialylated oligosaccharides Oli- solubility The degree to which a solute
gosaccharides that contain sialic acid can be dissolved in a defined solvent
(N-acetyl) neuramic acid are sialylated). (sometimes describes the opposite of
Sialic acid is often found as a terminal hydrophobicity).
residue of oligosaccharide chains of solute A substance that is dissolved
glycoproteins. Sialic acid imparts negative in a solvent; the part of a solution that is
charge to glycoproteins, because its car- uniformly dispersed in another substance.
boxyl group tends to dissociate a proton at somatic cell In higher organisms, a
physiological pH. cell that (unlike germ cells) carries the full
silica Silicon dioxide, SiO2, occurring genetic make-up of an organism.
naturally in crystalline, microcrystalline, and SOPs Standard operating procedures;
amorphous form; used to make glass and detailed (step-by-step), instructions to
ceramics, and used in pharmaceuticals. Silica achieve uniformity in the performance of a
gel is a jelly-like form of silicon dioxide specific process or piece of equipment, which
that is widely used as a solid medium, as a are approved by the quality control unit and
dehumidifying and dehydrating agent, and in used for GMP operations.
many chemical processes. Southwestern blot Analytical blotting
SIP Steam-in-place; using steam to clean technique for studying DNA-protein interac-
and sterilize equipment or systems without tions using labeled DNA to detect proteins
removing them from their installed location. transferred to membrane filters.
(See CIP) sparge To spray. A sparger is the
siRNA Small interfering RNA, short component of a fermentor that sprays air
interfering RNA, or silencing RNA; a class of into the broth.
20 to 25 nucleotide-long double-stranded species In chemistry, a particular kind of
RNA molecules that play a variety of roles in atomic nucleus, atom, molecule, or ion.
biology. Most notably, siRNA is involved in specifications Tests, analytical proce-
the RNA interference (RNAi) pathway, where dures, and appropriate acceptance criteria
it interferes with the expression of a specific that are numerical limits or ranges that
gene. (See RNAi) establish a set of criteria to which a raw
skid Common term for a complete chro- material, drug substance, or drug product
matography system on wheels. must conform to be considered acceptable
SMB Simulated moving bed; a method in for its intended use.
liquid chromatography of making separa- specificity The degree to which a
tions constant rather than in a batch process. substance exerts a definitive and distinctive

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[ BIOTERMINOLOGY ]

influence on a particular part of the body acteristic of a given product; stability profile
and on the course of a particular disease. means the types of chemical degradations,
spectrometry Spectroscopy methods rates, and expected shelf life that character-
related to measurements of mass. ize a product.
spectroscopy Study of the molecular stabilizer A chemical additive that
absorption of light using optics. Different helps maintain solution stability or drug
wavelengths and types of light can tell dif- product stability.
ferent things about the molecules identity staining A procedure of labeling tissues,
and condition. Proteins are often studied organisms, or molecules (such as DNA or
using fluorescence and infrared (see FT-IR) proteins) with colored or fluorescent dyes
spectroscopy. Fluorescence spectroscopy to allow visualization by microscopic or
induces molecules to emit light by the ap- macroscopic techniques.
plication of laser energy. starting material European term
spike Adding a known amount of analyte meaning raw materials used in cGMP
from a laboratory standard, sometimes manufacturing, but excluding components.
with something highly reactive (such as a (See component, active starting material,
radioactive or fluorescent dye) to act as a raw material)
tracer. Used to check a method for recovery statistical process control Monitoring
or accuracy. and controlling a process using statistical
sponsor Organization that takes primary analysis with the aim of managing variabil-
ownership and responsibility for a product, ity at critical process control steps.
and usually will be the license holder. A stereoisomer Any of a group of isomers
sponsor may outsource testing, clinical tri- in which atoms are linked in the same order
als, or manufacturing to other entities (CLO, but differ in their spatial arrangement.
CRO, CMO) but retains oversight of the pro- sterile Absolutely free of any microbio-
gram. The exact division of roles is specified logical contamination; an absolute state that
in contracts and in the quality agreement, a cannot be proven unless all of a material
key GMP document. is consumed in the test. In practical terms,
spray-drying Creation of a fine powder sterility assurance is demonstrated by
by passing a bulk or final drug formulation showing that less than 1 in 106 units may be
through a hot air stream to evaporate dis- contaminated. (See USP Sterility Test)
persed droplets; contrast with freeze-drying. stoichiometry The study of proportional
stability 1. Ability to maintain constant (quantitative) relationships between two or
characteristics in the presence of forces more substances during a chemical reaction.
that threaten to disturb them; resistance to strain A population of cells all descend-
change. Resistance to structural, chemi- ed from a single cell.
cal, and biological changes in composition structural isomers Any isobaric species
caused by such factors as light, temperature, that has the same elemental composition (and
and storage (shelf) time. 2. A defined char- assumed basic structure) but differs in the

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arrangement of the elements, often assumed plasmons (electromagnetic waves formed by


to be functional groups for biomolecules. electrons) propagating along the surface of a
subcutaneous Referring to the layer thin metal layer resonate with light coming
of tissue (subcutis) directly underlying the through a prism at a specific angle, stopping
cutis, which is mainly composed of adipose that light from reflecting. The electrical field
tissue. Subcutaneous (abbr: subq or sc) thus created is very sensitive to chemical
injections are given by injecting a fluid into changes (such as molecular interactions) in
the subcutis. It is relatively painless and an a solution interfacing with the surface, which
effective way to administer particular types causes specific measurable differences in the
of medication. Certain depot injections are angle of light necessary for the phenomenon
a solid or oil-based medication, which is ad- to perpetuate. SPR biosensors detect and
ministered subcutaneously where it releases measure those changes.
its agent slowly over a period of weeks. surfactant Any substance that changes
sublimation Passing directly from a solid the nature of a surface, such as lowering the
to a vapor state without first melting into a surface tension of water.
liquid. suspension Particles floating in (not
substrate Reactive material, the sub- necessarily on) a liquid medium, or the mix
stance on which an enzyme acts. of particles and liquid itself.
substratum The solid surface on which a sustained delivery Drug delivery in
cell moves or on which cells grow. which the duration of release, action, and
sulfation The formation of sulfuric acid bioavailability are controlled and reproduc-
esters from alcohols or olefins (synthetic ible; usually a depot (reservoir) of drug is
fibers, such as polypropylene). created in the body (at the injection site, for
sulfhydryl group Any compound of example), and the delivery matrix releases
sulfur and another element, usually made by the therapeutic molecules over a period of
direct reaction of the elements. time. Biodegradable polymers are under
supernatant Material floating on the study as microspheres and other methods of
surface of a liquid mixture (often the liquid sustained delivery for biomolecules.
component that has the lowest density); symbiotic Living together for mutual
the overlying fluid layer that remains after benefit.
precipitation of a solid component through synthesis Creating products through
centrifugation. chemical and enzymatic reactions. Biopro-
supercritical fluids Common gases, cessing lets living cells or organisms do this
such as carbon dioxide, when under pres- work.
sure contain a liquid form of the gas. This
liquid is useful in a variety of biotechnol-
ogy applications. TU
surface plasmon resonance A phenom- tangential flow filtration A separa-
enon used in analytical chemistry whereby tion method that transfers components

A Guide to the Biopharmaceutical Lexicon February 2012 57


[ BIOTERMINOLOGY ]

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.
target Organ, tissue, or molecule
involved in a disease that is modified or
affected by a potential therapeutic.
targeted delivery Drug delivery that is
specifically directed to the therapeutic mol-
ecules site of action by one of various means
such as a targeting monoclonal antibody In high-throughput laboratories, batches
of samples are processed for screening,
(that binds specifically to a particular kind of conrmation, or proling purposes.
receptor) or surgery (in which a drug formula-
tion is injected into a particular location, time-dependent change in viscosity.
such as the liver). throughput The movement of a material
T cell A synonym for T lymphocyte, T through a system; specifically, a measure of
cells are a type of leukocyte (white cells of the quantity of a substance passing through
the blood and lymphoid system) that (along a piece of equipment or section of a pipe or
with the less numerous B lymphocytes in the pump line during a specified time.
bloodstream) are necessary for conferring time-of-flight (TOF) mass spectrom-
antibody-independent cellular immunity. Of eter A mass analyzer that separates ions of
their subsets, cytotoxic or killer T cells can different mass-to-charge ratios by their time
kill cells bearing specific antigens, helper T of travel through a field-free vacuum region
cells can help B cells form antibodies, and after having been give the same kinetic
suppressor T cells suppress the activity of energy. The velocity of the ions is dependent
other cells involved in immune responses. on the mass-to-charge ratio and, as the
Team Biologics A partnership between ions are traveling over a fixed distance, the
FDAs Office of Regulatory Affairs (ORA) and time taken to reach the detector allows the
CBER to focus on inspection and compliance mass-to-charge ratios to be determined with
issues in biologics. Its goal is to ensure the heavier ions taking longer.
quality and safety of biologic products and tissue culture Growing plant or animal
resolve inconsistencies. tissues outside of the body, as in a nutri-
tertiary structure The three-dimensional ent medium in a laboratory; similar to cell
folding (its normal state) of a polypeptide culture, but cells are maintained in their
chain in a protein molecule. structured, tissue form.
Thr Threonine; one of more than 20 titer A measured sample. (To draw a
naturally occurring amino acids. measured, representative sample from a
thrixotropy The property of some non- larger amount is to titrate.)
Newtonian pseudoplastic fluids to show a TOC analysis Total organic carbon

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[ BIOTERMINOLOGY ]

analysis; an analytical method whereby by averaging over all possible collision


organic carbon is oxidized to produce CO2, geometries.
the amount of which produced is directly transcription Synthesis involving RNA
proportional to the amount of carbon present. polymerase of complementary RNA from a
Measurement of CO2, as a result, indicates sequence of DNA.
the presence of organic molecules. The bio- transdermal delivery Drug delivery
pharmaceutical industry uses TOC analysis to across the skin, accomplished without
test pure water and to evaluate and validate breaking the skin. For large molecules like
cleaning procedures. proteins and peptides, this is possible only
top-down sequencing The identification through iontophoresis.
and characterization of intact protein from transduction The transfer of genetic
tandem mass spectrometry experiments, material from one cell or another by means
enabling the identification of post-transla- of virus or phage vector.
tion modifications. The top-down approach transformation A change in the genetic
provides direct measurement of the intact structure of an organism by the incorporation
mass of the protein, as well as fragment of foreign DNA.
ion information relating to the amino acid transgenics The alteration of plant
sequence. or animal DNA so that it contains a gene
toxicology Study of harmful substances: from another organism. There are two
what they are composed of and which part is types of cells in animals and plants, germ
harmful, how they exert their effect, whether line cells (the sperm and egg in animals,
an antidote exists, and how the antidote pollen and ovule in plants) and somatic
works. cells (all of the other cells). Germ-line
trade secret any unpatented and/or DNA is altered in transgenic animals and
unpatentable trade-secret information and plants so those alterations are passed on
proprietary technology of any kind or nature to offspring. That is done to produce thera-
owned by a company, such as a process peutics, to study disease, and to improve
method, formulation, or other information livestock strains. Transgenic plants have
that adds value to a product or process. been created for increased resistance to
TM trajectory method; The trajectory disease and insects as well as to make
method treats the ion as a collection of biopharmaceuticals.
atoms, each one represented by a 12-6-4 translation The process by which
potential. The effective potential is obtained information transferred from DNA by RNA
by summing over the individual atomic specifies the sequence of amino acids in a
contributions; then trajectories are run in this polypeptide (protein) chain.
potential to obtain the scattering angle (the transmucosal delivery Drug delivery
angle between the incoming and departing across mucosal membranes, such as the
buffer gas atom trajectory). The orientation- nasal lining, the inside of the mouth, or the
ally averaged collision integral is determined rectal wall.

A Guide to the Biopharmaceutical Lexicon February 2012 59


[ BIOTERMINOLOGY ]

treatment IND An IND that makes a of many species, generally believed to be


promising new drug available to desperately caused by prions.
ill patients as early in the drug development turbidostat A variation on a chemo-
process as possible. FDA permits the drug to stat. Whereas a chemostat is designed for
be used if there is preliminary evidence of constant input of medium, a turbidostat is
efficacy and it treats a serious or life-threat- designed to keep the organisms at a constant
ening disease, or if there is no comparable concentration. A turbidity sensor measures
therapy available. the concentration of organisms in the culture
trehalose A sugar (non-reducing disac- and adds additional medium when a preset
charide) found in certain algae and plants, value is exceeded.
some bacteria, and some insects. It is used turbulent flow field The state that re-
as a preservative and stabilizer in some sults from mixing the contents of a fermentor
biopharmaceutical formulations. or bioreactor to provide oxygen to the cells.
trend A statistical term referring to the That must be balanced against the shear that
direction or rate of change of a variable(s). causes cell damage and death.
[From ICH Q9] turnkey system A piece of equipment,
trifluoroacetic acid A nonflammable, process train, or manufacturing plant that is
hygroscopic (takes up moisture), colorless delivered to the customer in a ready-to-run
liquid used as a reagent, solvent, catalyst, condition, specialized for the customers
and strong nonoxidizing acid. application, with no additional equipment or
tRNA Transfer RNA; a type of RNA with modifications required.
triplet nucleotide sequences that comple- TWIG travelling wave ion guide; the mech-
ment the nucleotide coding sequences of anism by which mobility is implemented in
mRNA. In protein synthesis, tRNA bonds an ion mobility capable mass spectrometer,
with amino acids and transfers them to the i.e., Waters SYNAPT Systems. Ions are
ribosomes, where proteins are assembled moved through a pressurized region by the
according to the genetic code carried by action of a continuous train of transient volt-
mRNA. age pulses, or travelling waves.
Trp Tryptophan; one of more than 20 Tyr Tyrosine; one of more than 20 natu-
naturally occurring amino acids. rally occurring amino acids.
trypsin An enzyme capable of cleaving ultrafiltration Filtration under pressure.
peptide bonds. It is used to remove adherent undercooling An uncommon method of
cells from a surface and to break up (digest) biomolecular preservation in which emul-
purified proteins for analysis. sions are used to cool the solution below its
tryptic fragment analysis Identifying freezing point without freezing.
and quantitating the peptides resulting from underflow The dewatered solids that re-
tryptic digestion. sult from compaction during centrifugation.
TSE Transmissible spongiform encepha- unfolding A form of protein degradation
lopathies; neurological disease in mammals in which the three-dimensional structure of

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a molecule unravels to something that more drugs to test for sterility. By itself, this test
closely resembles a basic chain of amino does not prove a given lot is sterile; rather,
acids. taken together with all other validation, GMP
unicellular A single-cell organism. controls, and product/process testing, it
unit operation A distinct chemical or increases confidence that a given lot is safe.
physical step in a downstream process, (See sterility)
such as ultrafiltration, centrifugation, or UV-vis Ultraviolet-visible spectroscopy;
chromatography. an analytical method that measures the
UPLC Technology The use of a high- absorption of light in the 200 to 750 nm
effiency LC system holistically designed range of the electromagnetic spectrum. It is
by Waters Corporation to accommodate used in determining protein concentration
sub-2 m particles and very high operating and is often applied to HPLC detection.
pressure is termed UltraPerformance Liquid
Chromatography. The major benefits of this
technology are significant improvements
in resolution over HPLC, and/or faster run VZ
times, while maintaining the resolution seen vaccines Preparations that elicit an im-
in an existing HPLC separation. mune response (production of antibodies) to
USP or USP-NF The United States Phar- protect a person or animal from a disease-
macopeial Convention, Inc.; establishes and causing agent.
disseminates officially recognized standards vacuolation In cell and tissue culture, ex-
of quality and authoritative information for cess fluid, debris (aggregates), or gas (from
the use in the manufacture and testing of sparging) can form inside a cell vacuole, a
drugs, excipients, and raw materials. Also cavity within the cell that can be relatively
called one of the compendia. Other compen- clear and fluid filled, gas filled (as in a
dia include, for example, Ph.Eur (Pharmaco- number of blue-green algae), or food filled
peia Europa), JP (Japanese Pharmacopeia). (as in protozoa).
The USP, which defined specifications for val Valine; one of more than 20 naturally
approved drugs as well as general methods occurring amino acids.
and guidances, merged with the NF, National validation 1. Documented evidence
Formulary, which focused on specifications that shows that an assay or process, when
for raw materials and excipients. General operated within specified ranges of critical
chapters are not legally binding, but specific parameters, has a high probability of meeting
chapters are considered to be binding, and specifications. 2. The process of determin-
defined USP methods are accepted by the ing the degree of validity; the procedures
FDA as an appropriate standard. involved in checking data for correctness,
USP sterility test A method defined compliance with standards, and conformance
in the USP and Ph.Eur, and considered with the requirement specifications. A series
acceptable for per-lot testing of parenteral of experiments performed using a pre-ap-

A Guide to the Biopharmaceutical Lexicon February 2012 61


[ BIOTERMINOLOGY ]

proved protocol that will generate adequate viral clearance step Process step which
documented evidence to support a claim of a separates a given class of virus, if any are
validated state. present, from the desired product. A clear-
vCJD Variant Creutzfeld-Jakob disease; ance factor may be estimated by performing
a fatal neurological disease in humans, scaled-down experiments using a model
believed to be caused by infection with a virus, to determine process capability.
prion that also causes bovine spongiform en- viral inactivation step Process step,
cephalopathy (BSE) or mad cow disease in which inactivates the activity of a given class
cattle. CJD, or classical CJD, is not caused by of virus to provide assurance of safety. An
the BSE agent, and its etiology is unknown. inactivation factor may be estimated by
vector The plasmid, virus, or other performing scaled-down experiments using a
vehicle used to carry recombinant DNA into model virus, to determine process capability.
the cell of another species. virus The simplest form of life: RNA or
venture capital Also risk capital; money DNA wrapped in a shell of protein, some-
invested in a small, young, or start-up times with a means of injecting that genetic
company that is perceived to have excellent material into a host organism (infection).
growth prospects but without other access Viruses cannot reproduce on their own, but
to capital markets. Venture capitalists gener- require the aid of a host (bacteria, plant, or
ally supply capital in return for substantial animal). The host cells synthesis is often
equity and/or a seat on the board of direc- inhibited by the infecting virus, which may
tors. Sometimes, they provide management or may not result in disease (more than
and other financial support to their investee 200 viruses are known to produce human
companies. disease). An individual virus particle is
Vero An established cell line derived from called a virion, and virions vary in structure,
the kidney of the African green monkey. complexity, and size (ranging from 20 to
vessel jacket A temperature control 25 nm or less to 2,000 nm or more). Six
method consisting of a double wall outside classes of virus are defined by whether they
the main vessel wall. Liquid or steam flows are single or double stranded, DNA or RNA,
through the jacket to heat (or cool) the fluid or positive or negative.
in the vessel. Because biopharmaceuti- virus-like particles Also RVLP (retrovi-
cal products are so sensitive and vessel rus-like particles); particles that resemble
jackets can cause uneven heating (hot or retroviruses, yet lack infectivity, and usually
cold spots), shell-and-tube or plate-and- are found in established lines of mammalian
frame heat exchangers are more common in cells. Cell bank characterization seeks to
biopharmaceutical production systems. determine whether viral activity is present,
viability The extent to which cells and as a means of assessing risk. Not present in
tissues are living. Cells can be metaboli- nonmammalian cells or cell lines.
cally viable even if they are not reproduc- viscosity Thickness of a liquid; deter-
tively viable. mines its internal resistance to shear forces.

62 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

warning letter The most serious FDA is usually made from a single vial of the
post-audit (after inspection) letter, notify- master cell bank, in which each vial has
ing a manufacturer of adverse inspection comparable contents and is expected to
findings and giving it 15 days to reply with perform consistently when introduced into a
a concrete plan for remediation. May or may process or assay. Both master and work-
not be associated with other actions, such ing cell banks are extensively tested and
as injunction, consent decree, or product characterized before use. Manufacturing
seizure. usually starts when a vial of working cell
washing (of a column) Flushing a bank is thawed and added to a reactor. (See
column with a large volume of a solvent or master cell bank)
buffering agent before selective elution of xenobiotic A chemical found in an organ-
the desired analyte. ism but which is not normally produced or
well-characterized A chemical entity expected to be present in it. It can also cover
whose identity, purity, impurities, potency, substances which are present in much higher
and quantity can be determined and con- concentrations than are usual. Specifically,
trolled; most well-characterized biologics drugs such as antibiotics are xenobiotics in
are recombinant DNA-derived proteins or humans because the human body does not
monoclonal antibodies. produce them itself, nor are they part of a
Western blot An immunochemical normal diet.
method for identifying proteins in a complex xenotransplantation Implantation of
mixture, proteins separated by electropho- living cells, tissues, or solid organs from
resis are transferred (blotted) from the gel one species into another, used when human
medium to a protein-binding nitrocellulose donors are unavailable or when a temporary
or polymeric membrane; the transferred or bridge organ is needed; a controversial
proteins are then detected by their relative practice given concerns about potential
binding to labeled antibodies. (See blotting) viral transmission and strong immuological
WFI Water for injection; very pure water reactions.
that meets specifications defined by the USP YAC Yeast artificial chromosome; a vector
or other compendia; suitable for parenteral used to clone DNA fragments up to 100,000
uses. base-pairs long. YACs are constructed from
withdrawal Product withdrawal; a recall the telomeric, centromeric, and replication
of a lot of product that is done voluntarily by sequences of yeast cells.
a firm, when there is concern about product yeast A single-celled fungus (eukary-
quality that is not proven. A recall may be ote).
mandated by FDA or regulatory bodies. (See
also recall) Waters, UltraPerformance Liquid Chromatography, and
WHO The World Health Organization; a UPLC are registered trademarks of Waters Corporation.
BiopharmaLynx, HDMS, High Definition Mass Spectrom-
United Nations organization. etry, MassLynx, SYNAPT, and The Science of Whats Pos-
working cell bank A cell bank that sible are trademarks of Waters Corporation.

A Guide to the Biopharmaceutical Lexicon February 2012 63


[ BIOTERMINOLOGY ]

suggested resources
If you are looking for additional information (or terms not included
in our glossary), here are some places to begin your search.

BOOKS Process Validation in Manufacturing of Biophar-


maceuticals, Anurag S. Rathore and Gail Sofer,
2006 Physicians Desk Reference (Thomson Eds. (CRC Press, Taylor & Francis Group, Boca
Healthcare, Montvale, NJ 2006) Raton, FL 2005)
Biopharmaceutical Drug Design and Develop- J.D. Watson, et al., Recombinant DNA, genes and
ment, S. Wu-Pong and Y. Rojanasakul, Eds. genomes: a short course. (Scientific American
(Humana Press Inc., Totowa, NJ 1999) Books, distributed by W.H. Freeman and Com-
pany, New York 2007)
W. Bains, Biotechnology from A to Z, 3rd ed.
(Oxford University Press, Oxford, UK 2004) ORGANIZATIONS
American Association of Pharmaceutical
Expediting Drug and Biologics Development: A Scientists, Arlington, VA
Strategic Approach, 3rd ed., Steven E. Linberg, aaps.org
Ed. (Parexel International Corporation, Waltham,
MA 2006) Biotechnology Industry Organization
Washington, DC; bio.org
FDA-Speak: A Glossary and Agency Guide, 2nd California Separation Science Society
ed. D.E. Snyder, Ed. (CRC Press, Boca Raton, FL San Francisco, CA
2001) casss.org
Handbook of Biopharma Industry Acronyms & FDA
Terms, Ronald P. Even, Ed, (Jones and Bartlett US Food and Drug Administration
Publishers, Sudbury, MA 2009) Rockville, Maryland
Center for Biologics Evaluation and Research,
J.F. Huxsoll, Quality Assurance for Biopharma- www.fda.gov/cber/index.html
ceuticals (John Wiley & Sons, Inc., New York Center for Drug Evaluation and Research,
1994) www.fda.gov/cder
Electronic Freedom-of-Information Reading
J.M. Walker and M. Cox, The Language of Room, www.fda.gov/foi/
Biotechnology: A Dictionary of Terms, 2nd ed.
(American Chemical Society, Washington, DC Health Canada
1995) Health Products and Food
Branch Inspectorate, Ottawa, ON
The Merck Index: An Encyclopedia of Chemicals, hc-sc.gc.ca
Drugs, and Biologicals,14th Edition (Merck & Co., The International Conference on Harmoniza-
Inc., Whitehouse Station, NJ, 2006) tion of Technical Requirements for Registra-
tion of Pharmaceuticals for Human Use
The Merck Manual of Medical Information Second Geneva, Switzerland
Home Edition (Merck & Co., Inc., Whitehouse ich.org
Station, NJ 2003)
International Pharmaceutical Excipient Council
P. Singleton and D. Sainsbury, Dictionary of of the Americas
Microbiology and Molecular Biology, 3rd ed. Arlington, VA
(John Wiley & Sons, New York 2002) ipecamericas.org

64 February 2012 A Guide to the Biopharmaceutical Lexicon


[ BIOTERMINOLOGY ]

International Society for Pharmaceutical Engineering Manufacturers & Associations


Tampa, FL
www.inpharm.com
ispe.org
InPharm
National Center for Biotechnology Information www.intelihealth.com
National Library of Medicine Aetna InteliHealth
Bethesda, MD
ncbi.nlm.nih.gov www.medicinenet.com/Script/Main/hp.asp
MedicineNet.com. See Med Term dictionary from
Parenteral Drug Association the home page
Bethesda, MD
www.medscape.com
pda.org
MedScape
www.bioethics.upenn.edu
WORLDWIDE WEB SITES Bioethics.Net
www.antibodyresource.com www.merck.com/pubs
The Antibody Resource Page Merck publications online (searchable)

www.biotechinstitute.org users.path.ox.ac.uk/~scobbold/tig/new1/
The Biotechnology Institute mabth.html
A Hundred Years of Antibody Therapy
www.online-medical-dictionary.org
www.mtdesk.com
The Online Medical Dictionary
Alphabetical index of terminology: new drugs,
whatis.techtarget.com equipment, and procedures
TechTargets glossary of IT-related words www.ncbi.nlm.nih.gov
NCBIs PubMed
www.nationalhealthmuseum.org
The National Health Museum online www.genome.gov
Glossary of Genetic Terms from the National
www.biospace.com Human Genome Research Institutes division of
BioSpace intramural research

www.bioworld.com www.ornl.gov/TechResources/Human_
BioWorld Online Genome/glossary
Human Genome Projects genome glossary
www.chem.vt.edu/chem-ed/ac-meths.html www.pharma-lexicon.com/index.php
Encyclopedia of Analytical Instrumentation from MediLexicon
the Virginia Techs Chemistry Hypermedia Project
www.ncbi.nlm.nih.gov
www.emea.europa.eu National Center for Biotechnology Information
European Medicines Agency
www.pdr.net
www.geneed.com/glossary/index.html PDR.Net
GeneEds biotechnology glossary www.expasy.org
www.genomicglossaries.com Swiss Institute of Bioinformatics
Genomics Glossary by Cambridge Healthtech www.webmd.com
Institute Web MD
ifpma.org www.whybiotech.com
International Federation of Pharmaceutical Council for Biotechnology Information

A Guide to the Biopharmaceutical Lexicon February 2012 65


[ BIOTERMINOLOGY ]

PEER REVIEWED PUBLICATIONS FEATURING WATERS TECHNOLOGY


Gilar M, Yu YQ, Ahn J, Xie H, Han H, Ying lens JHM, Rosing H, Beijnena JH. Electro-
W, Qian X. Characterization of glycoprotein spray ionization quadrupole ion-mobility
digests with hydrophilic interaction chromatog- time-of-flight mass spectrometry as a tool
raphy and mass spectrometry. Anal Biochem. to distinguish the lot-to-lot heterogeneity in
2011 Oct 1;417(1):80-8. Epub 2011 May 27. N-glycosylation profile of a therapeutic mono-
clonal antibody. J Am Soc Mass Spectrom.
Xie H, Doneanu C, Chen W, Rininger J, Mazzeo
2009;20(10):202133.
JR. Characterization of a Recombinant Influenza
Vaccine Candidate Using Complementary LC-MS Chakraborty AB, Xie H, Skilton SJ, Gebler JC,
Methods. Curr Pharm Biotechnol. 2011 May 5. Chen W. Improving the analytical workflow for
protein biopharmaceutical characterization with
Gilar M, Jaworski A. Retention behavior of
a novel LC-MS system solution. Curr Trends in
peptides in hydrophilic-interaction chro-
Mass Spectrom. 2009;Jul.
matography. J Chromatogr A. 2011 Dec
9;1218(49):8890-6. Epub 2011 Apr 12. Xie H, Gilar M, Gebler JC. Characteriza-
Ivleva VB, Yu YQ, Gilar M. Ultra-performance tion of protein impurities and site-specific
liquid chromatography/tandem mass spectrom- modifications using peptide mapping with
etry (UPLC/MS/MS) and UPLC/MS(E) analysis liquid chromatography and data independent
of RNA oligonucleotides. Rapid Commun Mass acquisition mass spectrometry. Anal Chem.
Spectrom. 2010 Sep 15;24(17):263140. 2009;Jun 11.

Xie H, Chakraborty A, Ahn J, Yu YQ, Dakshin- Yu YQ, Fournier J, Gilar M, Gebler JC. Phospho-
amoorthy DP, Gilar M, Chen W, Skilton SJ, peptide enrichment using microscale titanium
Mazzeo JR. Rapid comparison of a candidate dioxide solid phase extraction. J Sep Sci.
biosimilar to an innovator monoclonal anti- 2009;32:118999.
body with advanced liquid chromatography and Doneanu CE, Chen W, Gebler JC. Analysis of
mass spectrometry technologies. MAbs. 2010 heparin-derived oligosaccharides with ion-pair
Jul 6;2(4). reversed-phase chromatography and mass spec-
Ahn J, Bones J, Yu YQ, Rudd PM, Gilar M. trometry. Anal Chem. 2009;81:348599.
Separation of 2-aminobenzamide labeled gly- Chakraborty AB, Chen W, Gebler JC. Im-
cans using hydrophilic interaction chromatog- proved mass determination of poly (ethylene
raphy columns packed with 1.7 mum sorbent. J glycols) by electrospray ion-mobility
Chromatogr B Analyt Technol Biomed Life Sci. time-of-flight mass spectrometry coupled
2010 Feb 1; 878(34):403-8. with ionmolecule reactions. Pharm Technol.
Gilar M, Xie H, Jaworski A. Utility of 2008;32(7):8087.
retention prediction model for investigation Olivova P, Chen W, Chakraborty AB, Gebler
of peptide separation selectivity in reversed- JC. Determination of N-glycosylation
phase liquid chromatography: Impact of sites and site heterogeneity in a monoclo-
concentration of trifluoroacetic acid, nal antibody by electrospray quadrupole
column temperature, gradient slope and ion-mobility time-of-flight mass spec-
type of stationary phase. Anal Chem. trometry. Rapid Commun Mass Spectrom.
2010;82:265275. 2008;22(1):2940.
Doneanu CE, Chen W. Impurity Evaluation of
Gilar M, Yu YQ, Ahn J, Fournier J, Gebler
Heparin Sodium by Anion Exchange Chromatog-
JC. Mixed-mode chromatography for frac-
raphy. American Laboratory. 2009;Oct:269.
tionation of peptides, phosphopeptides, and
Damen CWN, Chen W, Chakraborty AB, van sialylated glycopeptides. J Chromatogr A.
Oosterhout M, Mazzeo JR, Gebler JC, Schel- 2008;1191:16270.

66 February 2012 A Guide to the Biopharmaceutical Lexicon

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