Home » Pharmaceutical Glossary » Glossary of Terms - C

Where ion = magnesium, calcium, or other elements that contribute to hardness.

Calibration
A comparison of a measurement standard or instrument of unknown accuracy to detect, correlate, report, or eliminate by adjustment of any variation in the accuracy of the unknown standard or instrument.

Calibration (ICH API defintion)
The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.

Calorie
Any of several approximately equal units of heat, each measured as the quantity of heat required to raise the temperature of one (1) gram of water by °C from a standard initial temperature, specially from 3.98°C, 14.5°C, or 19.5°C, at a constant pressure of one (1) atmosphere. Also called "gram calorie", "small calorie".
The unit of heat equal to 1/100 the quantity of heat required to raise the temperature of one (1) gram of water from 0°C to 100°C at one (10 atmosphere pressure. Also called "mean calorie".
The unit required to raise the temperature of one (1) Kilogram of water by 1°C at one (1) atmosphere pressure. Also called "kilogram calorie", "large calorie".

Calorimetry
Analytical method that measures heat loss or gain resulting from physical or chemical changes in a sample. Differential scanning calorimetry compares the results of heating a sample to those for heating a reference material. For example, a method to measure the temperature at which the sample crystallizes, changes phases, or decomposes.

Cancer
The name given to a group of diseases that are characterized by uncontrolled cellular growth.

Capsid
The external protein shell or coat of a virus particle.

Carbohydrates
A large class of carbon-hydrogen-oxygen compounds that includes the sugars and their polymers (mainly starch, glycogen and cellulose). Most carbohydrates are produced by photosynthesis in plants. They are the major food compounds for both plants and animals. One group of carbohydrates, cellulose, is the primary structural material of plants.

Carbon Filter
A vessel loaded with activated carbon and used to remove organics, chlorine, tastes, and odors from liquids, operating on the principle of adsorption.

Carbon Thickness
A measurement of surface organic material. Carbon thickness values typically range from 5 to 20 angstroms (Å). Significantly contaminated surfaces can show surface carbon thickness of 20 angstroms (Å) or more.

Carbonate Hardness
That hardness in water caused by bicarbonates and carbonates of calcium and magnesium. If alkalinity exceeds total hardness, all hardness is carbonate hardness; if hardness exceeds alkalinity, the carbonate hardness equals the alkalinity.

Carcinogen
A substance that causes the development of cancerous growths in living tissue. A chemical is considered to be a carcinogen if it has been evaluated by the International Agency for Cancer Research (IARC) and found to be a carcinogen or potential carcinogen, or if it is listed in the Annual Report on Carcinogens published by the National Toxicology Program, or if it is regulated by OSHA as a carcinogen.

Carcinogenic
Cancer-causing. Many agents that are carcinogenic are mutagens.

Carrier
A person who has a recessive mutated gene, together with its normal allele. Carriers do not usually develop disease but can pass the mutated gene on to their children.

Catabolism
The intracellular phase of metabolism involved in the energy-yielding degradation of nutrient molecules (for example, glucose to CO2 and H2O). Waste products are called catabolites.

Catalase
An enzyme that catalyzes the decomposition of hydrogen peroxide and molecular oxygen and water.

Catalyst
A compound that increases the rate of a chemical reaction without being consumed or changed. In the biosciences, the term enzyme is used. Enzymes catalyze biological reactions.

Cation
A positively charged particle or ion.

Cation Exchange
The displacement of one positively charged particle by another on a cation-exchange material.

Cation Exchange Resin
An Ion exchange resin, which removes positively charged ions (cations) by exchanging them for hydrogen ions.

Cavitation
A condition of liquid flow where, after partial vaporization of the liquid, the subsequent collapse of vapor bubbles can produce surface damage.

CBER
(also see: center for Biologics Evaluation and Research)

Center For Biologics Evaluation and Research (CBER)
The FDA successor to the Bureau of Biologics concerned with biologic drugs, and most importantly, with the new protein and peptide drugs emanating from biotechnology.

Center For Drug Evaluation and Research (CDER)
The successor to the Bureau of Drugs of the FDA concerned with all SVPs (Small Volume Parenterals), LVPs (Large Volume Parenterals), and non-biological drugs.

Certified Vendor Drawings
Drawings prepared by vendors for the fabrication of equipment, specialty components and skid mounted systems. These are certified as fabricated by the vendor and become the official document for the equipment involved.

Celsius
Of or pertaining to a temperature scale that registers the freezing point of water as 0°C and the boiling point as 100°C under normal atmospheric pressure. Also called "centigrade". The designation Celsius has been official since 1948, but centigrade remains in common use.

Cell
The fundamental unit of life. The living tissue of almost every organism is composed of these fundamental living units. Unicellular organisms, such as yeast or a bacterium, perform all life functions within the one cell. In a higher organism, a multicellular organism, entire populations of cells may be designated a particular task. The cells of muscle tissue, for example, are specialized for movement.

Cell Bank
Master Cell Bank: The bank of cells, which contain the original unused mutated cells from which, the Manufacturing Working Cell Bank is taken. This is usually kept under lock with very limited access.

Manufacturing Working Cell Bank: The bank of cells derived from the Master Cell Bank, which are used to seed the fermentation manufacturing process.

Cell Culture
The in vitro propagation of cells removed from organisms in a laboratory environment that has strict sterility, temperature, and nutrient requirement; also used to refer to any particular individual sample. Usually, cell culture takes place in a bioreactor.

Cell Differentiation
The process whereby descendants of a common parental cell achieve and maintain specialization of structure and function. Muscle cells become muscle cells and bone cells develop. In humans all the different types of cells differentiate from the simple sperm and egg.

Cell Fusion
The fusing together of two or more cells to become a single cell. This technique has had important consequences in immunology, developmental biology, and genetics. For example, monoclonal antibodies are produced by fusing a spleen cell (producing an antibody specific for the antigen of interest) with a mouse myeloma cell to produce a hybridoma which has an indefinitely long life because of the myeloma component and which secretes a specific antibody. When a human cell is fused with a mouse cell, the human chromosomes are progressively lost from the resultant hybrid and by correlating the presence of proteins in the hybrid with the presence of particular human chromosomes, genes can be assigned to individual chromosomes.

Cell Lines
When cells from the first culture (taken from the organism) are used to make subsequent cultures, a cell line is established. "Immortal" cell lines can replicate indefinitely.

Cellulose
A polymer of six-carbon sugars found in all plant matter, the most abundant biological compound on earth.

Centimorgan (cM)
A unit of measure of recombination frequency. One centimorgan is equal to a 1% chance that a marker at one genetic locus will be separated from a marker at a second locus due to crossing over in a single generation. In human beings, one centimorgan is equivalent, on average, to one million base pairs.

Centrifugation
Mechanical means of separation based on differences in sedimentation rates due to differences in density between the suspended particles in the liquid.

Centrifuge
A centrifuge operates on the principle of centrifugal force, the inertial reaction by which a body tends to move away from a center about which it revolves. This technique is commonly used to separate solids from liquids or liquids of different densities. Centrifugal equipment is divided into two major types, sedimenters and filters:

Sedimenters
For sedimentation, batch and continuous centrifuges are available. There are three types of centrifuges for continuous sedimentation.

a) Disc - constructed on the vertical axis, disc centrifuges are solid-bowl units. All are capable of separating liquids from solids, solids from two immiscible liquids and two immiscible liquids. Disc-stack centrifuges differ in their ability to handle different volumes of solids in the feed stream, and in the way that the separated solids are removed from the separation vessel: solids-retaining, solids-ejecting, and nozzle-bowl separators.

b) Decanters - consists of a cylindrical settling section with a tapered end. Inside the bowl is a scroll conveyor that is driven usually at a slightly faster rate than the bowl and can be controlled by a differential speed device or back drive.

c) Tubular - a vertical solid-wall cylinder provided with caps on both ends; a tubular centrifuge generally has a bottom feed inlet. When two liquids of different specific gravities are fed, the heavier phase is concentrated against the wall, while the lighter phase "floats" on the heavier phase.

Filters

Filtering centrifuges accommodate a range of liquid-solid separations. The two batch types, basket and peeler centrifuges, can separate almost any liquid-solid slurry. For continuous operation, there are pusher and conical centrifuges.

a) Pusher - with a horizontal axis, the pusher centrifuge operates at a constant fixed speed. It has a perforated bowl, generally with a bar-type screen. One end of the bowl is open while the opposite end is closed with a reciprocating diaphragm, or disc, which rotates with the bowl.

b) Conical - the standard conical centrifuge consists of a cone with a small closed end and a large open end to which is attached a coarsely woven drainage screen, topped with a filter screen or perforated plate. A compartmentalized casing surrounds the bowl. There are two variations of the basic conical centrifuge: the tilting conical centrifuge and the conveyor conical type.

Centromere
A specialized chromosome region to which mitotic or meiotic spindle fibers attach during cell division.

Certification
Documented testimony by qualified authorities that a system qualification, calibration, validation, or revalidation has been performed appropriately and that the results are acceptable. Personnel certification is proof that a person has achieved a certain level of qualification.

CFR (Code of Federal regulations) Title 21
The U.S. regulations that directly apply to biopharmaceutical development are contained in Title 21 parts 58 (Good Laboratory Practice for Nonclinical Laboratory Studies), 210 (Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General), 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals), and 600 (Biological Products: General).
Parts 50 (Protection of Human Subjects), 56 (Institutional Review Boards), and 312 (Investigational New Drugs) apply to critical trials.
Part 11 provides criteria which will consider electronic records to be equivalent to paper records and electronic signatures to be equivalent to traditional handwritten signatures. (also see: cGMPs (current Good Manufacturing Practices))

CFU (Colony Forming Unit)
A measure of the number of bacteria present in the environment or on the surfaces of an aseptic processing room, measured as part of qualification and ongoing monitoring. Also applied to the testing of purified water samples.

cGMPs (current Good Manufacturing Practices)
Current accepted standards of design, operation, practice, and sanitization. The FDA is empowered to inspect drug-manufacturing plants in which drugs are processed, manufactured, packaged, and stored for compliance with these standards.

Change Control
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated process's status. The intent is to determine the need for action that would ensure that the system is maintained in a validated state.

Change Over
The program by which a processing area is cleared of supplies and components used in the manufacture of a previous product and then readied for production of a new product. This often includes parts change over and/or special cleaning to eliminate cross-contamination.

Channeling
Cleavage, cracking, and furrowing of a resin bed due to resin age, a change in one of the feed solutions, or faulty operational procedures. The solution being treated follows the path of least resistance, runs through these furrows, and fails to contact active resin material in other parts of the bed.

Characterization
Precisely deciphering and describing all the characteristics of a drug substance that affect its efficacy and its purity. Or the chemical, physical, and sometimes biological properties that are attributes of a specific drug substance.

Checksum
A record of the number of bits transmitted and included with the transmission so that the receiving program can check to see whether the same number of bits arrived. If the counts match, it is assumed that the complete transmission was received.

Chelating Agents
Organic compounds that can withdraw ions from solution, forming insoluble complexes.

Chemoautotrophs
Facultative autotrophs that obtain their energy from the oxidation of inorganic compounds.

Chemostat
A growth chamber that keeps a bacterial culture at a specific volume and rate of growth by limiting nutrient medium and removing spent culture.

Chemotherapy
Treatment of disease by means of chemical substances or drugs.

Chimeric
An organism, especially a plant, containing tissues from at least two genetically distinct parents. Type of antibody, partially human and partially mouse.

Chloramine
A chlorine compound formed by reaction with organic amines or ammonia.

Chlorinated Vinyls
Thermoplastic chlorinated vinyls include PVC, CPVC, and VDC. PVC and CPVC are very similar materials, the primary difference being the addition of more chlorine to the PVC molecule to synthesize CPVC. This results in a higher glass transition temperature that equates to a higher use temperature for CPVC. The polymerization with chlorine also makes these materials inherently flame resistant. In addition to being resistant to higher temperatures, CPVC is more resistant to process chemicals.

Chlorination
Adding chlorine or chlorine compounds to water for disinfection.

Chlorine
An element used to kill microorganisms in water. At room temperature and atmospheric pressure a greenish yellow gas.

Chlorine Demand
Amount of chlorine used up by reacting with oxidizable substances in water before chlorine residual can be measured.

Chlorine Residual
Portion of free or combined chlorine that remains active after specified contact period.

Chloroplasts
Relatively large, chlorophyll containing, green organelles responsible for photosynthesis in photosynthetic eukaryotes, such as algae and plant cells. Every chloroplast contains an outer membrane and a large number of inner membranes called thylakoids.

CHO (Chinese Hamster Ovary) Cells
In cell culture, the cells of a female hamster's reproductive organs, which historically have proven to be excellent expression systems in analytical studies and for producing pharmaceutical proteins.

Chromatids
Copies of a chromosome produced by replication.

Chromatin
The complex of DNA and protein in the nucleus of the interphase cell, originally recognized by its reaction with stains specific for DNA.

Chromatography
Procedure by which solutes (e.g., proteins and other chemical products) are selectively separated by a dynamic differential migration process in a system consisting of two or more phases, one of which moves continuously in a given direction and in which the individual substances exhibit different mobilities by reason of differences in adsorption, partition, solubility, vapor pressure, molecular size, or ionic charge density. The individual substances thus obtained can be identified or determined by analytical methods. There are several types of chromatography in use with different operating principles:

1. Adsorption - separates products by their different affinities for the surface of a solid medium, either an inorganic carrier such as silica gel, alumina, or hydroxyapatite, or an organic polymer.

2. Ion Exchange - uses ion exchange resin to which ionized functional groups have been attached. At an appropriate pH, target proteins acquire a net surface charge that allows them to selectively bind to an ion exchange resin. Other impurities are eluted through the column.

3. Gel Filtration - employs a neutral cross-linked carrier with a defined pore size for molecular fractionation. Molecules larger than the largest pores cannot enter the matrix and pass directly through the column; smaller molecules enter the carrier and are retarded. Gel filtration thus separates on the basis of molecular size, eluting larger molecules first, followed by progressively smaller species.

4. Affinity - relies on the propensity of each biomolecule to have an affinity for another highly specific biomolecule, such as an antibody-antigen relationship. Once bound together, the drug molecules can be detached by altering various chemical attributes in the column.

5. Hydrophobic - separates by molecule polarity and reverse interaction with water.

6. High Pressure Liquid Chromatography (HPLC)-

Chromium Enrichment Layer Thickness
In stainless steel, the same as its maximum depth of enrichment, unless a surface iron layer is present in which case the chromium enrichment layer is calculated as the maximum depth of enrichment minus the thickness of the surface iron oxide layer.

Chromosome
The self-replicating genetic structure of cells containing the cellular DNA that bears in its nucleotide sequence the linear array of genes. In prokaryotes, chromosomal DNA is circular, and the entire genome is carried on one chromosome. Eukaryotic genomes consist of a number of chromosomes whose DNA is associated with different kind of proteins.

CIP (Clean In Place)
Internally cleaning a piece of equipment without relocation or disassembly. The equipment is cleaned but not necessarily sterilized. The cleaning is normally done by acid, caustic, or a combination of both, with WFI rinse. The design of a CIP system should considered the operating volume design for the water consumption, chemical and biowaste effluent, and energy required to clean a given circuit or piece of equipment.

Class 100
Classification of an aseptic processing area where particle count should not exceed 100 particles (3,530 particles per cubic meter) 0.5µm or larger, per cubic foot of air, and no more than 0.1 CFU (Colony Forming Units) per cubic foot. Target uniform air velocity is 90 fpm plus or minus 20%, HEPA filtered air. (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes)

Class 1,000
Classification of an area where particle count should not exceed 1,000 particles (35,300 particles per cubic meter) 0.5µm or larger, per cubic foot of air. Supplied by HEPA filtered air. Class 1,000 is not a pharmaceutical GMP expectation. (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes)

Class 10,000
Classification of an area where particle count should not exceed 10,000 particles (353,000 particles per cubic meter) 0.5µm or larger, per cubic foot of air. Minimum of 20 air changes per hour, HEPA filtered air. (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes)

Class 100,000
Classification of an area where particle count should not exceed 100,000 particles (3,530,000 particles per cubic meter) 0.5µm or larger, per cubic foot of air, and no more than 2.5 CFU (Colony Forming Units) per cubic foot. Minimum of 20 air changes per hour of HEPA filtered air. (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes) 

Class Name
"For naming and describing the classes, SI names and units are preferred; however, English (U.S. customary) units may be used". Federal Standard 209E superseded by ISO 14644-1). (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes) 

Class 95% ASHRAE Area
This area designation refers to the efficiency of the filters based on ASHRAE standard 52-76. These areas would have 95% efficient supply air filtration, unlike classified areas, which would have HEPA filtration. This classification is not specified in Federal Standard 209E or ISO 14644-1.

Class 65% ASHRAE Area
This area would have 65% efficient filtration. This classification is not specified in Federal Standard 209E or ISO 14644-1.

Class 30% ASHRAE Area
This area would have 30% efficient filtration. This classification is not specified in Federal Standard 209E or ISO 14644-1.

Classical Pharmaceuticals
Small-molecule, nonbiotech drugs produced by chemical synthesis.

Classification
The level (or the process of specifying or determining the level) of airborne particulate cleanliness applicable to a cleanroom or clean zone, expressed in terms of an ISO Class N, which represents maximum allowable concentrations (in particles per cubic meter of air) for considered sizes of particles. ISO 14644-1 (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes)

Classified Space
A space in which the number of airborne particles is limited. This is accomplished by the strict use of HVAC systems. Areas are classified as Class 10, Class 100, Class 1,000, Class 10,000, and Class 100,000. In pharmaceutical production, only classes 100, 10,000, and 100,000 are used. (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes)

Clean Air Device
Stand-alone equipment for treating and distributing clean air to achieve defined environmental conditions.

Clean Air Projector 
Fan and filter unit used to locally clean room air and deliver it to a desired location. Often called a fan/filter unit.

Clean Area
An area where particulate and microbial levels are specified (e.g., Filling Room - Class 10,000 "In Operation")

Clean In Place (CIP)
(also see: CIP (Clean In Place))

Cleanroom
A specially constructed space environmentally controlled with respect to airborne particles (size and count), temperature, humidity, air pressure, airflow patterns, air motion, and lighting. ISO 14644-1 defines it as "a room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the room, and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary." (also see Table I, Section II - Comparison of Airborne Particulate Cleanliness Classes) 

Cleanroom Classification
The maximum number of particles greater than or equal to 0.5µm in diameter that may be present in a cubic foot of room air.

Clean Space
A room or volume controlled to meet a certain airborne particulate limit (Class or Grade). In pharmaceutical facilities, clean spaces are usually classified and controlled only for aseptic processing facilities, but may also be defined for certain biotech processes. Final non-sterile bulk facilities, oral product, most topical product manufacturing facilities, and warehouses are normally not classified as clean spaces.

Clean Steam
Steam free from boiler additives that may be purified, filtered, or separated. When condensed, clean steam meets the specification for WFI. Usually utilized to sterilize process equipment.

Clean Zone
ISO 14644-1 defines it as "a dedicated space in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the zone and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary". Additionally, ISO 14644-1 states, "this zone may be open or enclosed and may or may not be located within a cleanroom".

Cleavage
The splitting up of a complex molecule into two or more simpler molecules. The series of cell divisions occurring in the ovum immediately following its fertilization.

Clinical Endpoint
An indicator (such as blood pressure) measured in a human subject to asses the safety, efficacy, or other objective of a clinical trial.

Clinical Hold
The temporary cessation of a clinical trial by FDA if the agency is concerned about a drug or study protocol. The trial may resume when the problem is solved.

Clinical Trials
Testing of INDs (Investigational New Drugs) in human subjects to prove safety and efficacy prior to the drug's approval for marketing. The investigation of a previously untested drug is generally divided into three phases:

1. Phase I: Introducing the product (or drug) into a small number, generally 20 to 80, patients or healthy volunteers to determine the drug's metabolism, pharmacological actions, and side effects associated with increasing doses.

2. Phase II: introducing the product (or drug) into a small number, generally no more than several hundred, patients with the disease or condition under study to evaluate the effectiveness of the drug, common short-term side effects and risks associated with its use.

3. Phase III: Introducing the product (or drug) into several hundred to several thousand subjects. Studies are expanded controlled and uncontrolled trials performed after preliminary evidence suggesting effectiveness of the drug has been obtained. If the results of the Phase III Clinical Trials are favorable, then the FDA will normally license the drug for manufacture and sale. This phase is usually performed using double blind studies with a placebo and the actual drug.

4. Phase IV: Ongoing testing studies conducted after the drug is approved. This is done to ensure the long-term efficacy of the drug, detect any long-term beneficial and/or detrimental side effects, and to determine additional potential uses for the drug

Clone
A population of genetically identical cells derived from the multiplication of a single cell. It is the basis of rDNA and monoclonal antibody production.

Clone
A group of individuals produced from one individual through asexual processes that do not involve the interchange or combination of genetic material. As a result, members of a clone have identical genetic compositions. Protozoa and bacteria, for example, frequently reproduce asexually by a process called binary fission. In binary fission, a single-celled organism undergoes cell division and the result is two cells with identical genetic composition. Next, these two identical cells undergo division and the result is four cells with identical genetic composition. These identical offspring are all members of a clone.

Cloning
Using specialized DNA technology (also see: Cloning Vector) to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. This process is used by researchers in the Human Genome Project, and is referred to as cloning DNA. The resulting cloned (copied) collections of DNA molecules are called clone libraries. A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. A third type of cloning produces complete, genetically identical animals such as the famous Scottish sheep, Dolly.

Cloning Vector
DNA molecule originating from a virus, a plasmid, or the cell of a higher organism into which another DNA fragment of appropriate size can be integrated without loss of the vectors capacity for self-replication; vectors introduce foreign DNA into host cells, where it can be reproduced in large quantities. Examples are plasmids, cosmids, and yeast artificial chromosomes; vectors are often recombinant molecules containing DNA sequences from several sources.

Closed System
One in which by its design and proper operation, prevents release of a microbiological agent or eukaryotic cell contained therein.

Closed System
System sterilized-in-place or sterilized while closed prior to use, is pressure or vacuum tight to some predefined leak rate, can be utilized for its intended purpose without breach to the integrity of the system, can be adapted for fluid transfers in or out while maintaining asepsis, and is connectable to other closed systems while maintaining integrity of all closed systems. (From PDA TR-28 for sterile product manufacture)

Clostridium
A genus of bacteria, most are obligate anaerobes and form endospores.

cM
(also see: Centimorgan)

Coagulation
Adding insoluble compounds to water to neutralize the electrical charge on colloids, causing them to coalesce to form larger particles that can be removed by settling.

Coaguligand
A VTA (Vascular Targeting Agent) that utilizes a human coagulation protein to induce tumor blood vessel clotting.

Coccus
A bacterium of round, spheroidal, or ovoid form, including micrococcus, staphylococcus, streptococcus, and pneumococcus.

COD (Chemical Oxygen Demand)
The amount of oxygen needed to completely oxidize all oxidizable organic and inorganic substances in water.

Coding Sequence
The region of a gene (DNA) that encodes the amino acid sequence of a protein.

Coenzyme
A non-polypeptide molecule required for the action of certain enzymes; often contains a vitamin as a component.
Cofactor
Small molecular weight, heat stable inorganic or organic substance required for the action of an enzyme.

Coliform Bacteria
A group of bacteria found in mammalian intestines and soil, used as a measure of fecal pollution in water. They are easy to identify and count in the laboratory because of their ability to ferment lactose.

Colonoscopy
Examination of the colon through a flexible, lighted instrument called a colonoscope.

Colony
A growth of microorganisms on a solid medium. The growth is visible without magnification.

Collagen
An albuminoid present in connective tissue, bone (ossein), and cartilage (chondrin), notable for its high content of the imino acids proline and hydroproxilone. On boiling with water it is converted into gelatin.

Collateral Targeting
The therapeutic strategy of targeting structures and cell types other than cancer cells common to all solid tumors as a means to attack a solid tumor.

Colloid
A translucent, yellowish material of the consistency of glue, less fluid than mucoid or mucinoid, found in the cells and tissues in a state of colloid degeneration or colloid carcinoma.
A substance, such as gelatin or cytoplasm that because of the size of its molecules, is slowly diffusible rather than soluble in water and is incapable of passing through an animal membrane.

Colloids
Particles so fine they will not settle without prior coagulation. They range from 10 Å to 1,000 Å (Angstroms). They have a net negative charge and readily clog membranes and foul resin beds. Examples are bacteria, silica, and clay.

CMC (Chemistry, Manufacturing, and Controls)
The section on a BLA (Biologics License Application) or IND (Investigational New Drug) describing the composition, manufacture, and specifications of a drug product and its ingredients.

Combustible Dust
Any finely divided solid material that is 420µ or 0.017 inches or less in diameter, or any material capable of passing through an US No. 40 standard sieve that when dispersed in air in the proper proportions, could be ignited by a flame, spark or other source of ignition.

Combustible Liquid
A liquid having a closed cup flash point at or above 100°F (37.8°C). Combustible liquids do not include compressed gases or cryogenic fluids. Combustible liquids are subdivided as follows:

1. Class II - Liquids having a closed cup flash point at or above 100°F (37.8°C) and below 140°F (60°C)

2. Class III-A - liquids having a closed cup flash point at or above 140°F (60°C) and below 200°F (93.3°C)
Class III-B - liquids having a closed cup flash point at or above 200°F (93.3°C).

Commissioning
A prescribed number of activities designed to take equipment and systems from static, substantially complete state to an operable state.

Commissioning
The documented process, verifying that equipment and systems are installed according to specifications, placing the equipment and systems into active service and verifying its proper operation. Commissioning is done for good business, but can include many Qualification activities.

Complementary DNA (cDNA)
DNA that is synthesized from a messenger RNA template; the single-stranded form is often used as a probe in physical mapping.

Complementary Sequence
Nucleic acid base sequence that can form a doublestranded structure by matching base pairs with another sequence; the complementary sequence to GTAC is CATG.

Compounding
The bringing together of excipient and solvent components into a homogeneous mix of active ingredients.

Compressed Gas
A material, or mixture of materials that are either liquefied, nonliquefied, or in solution having a boiling point of 68°F (20°C) or less at 14.7 psia (101.3 kPa) of pressure. The exceptions to this rule are those gases that have no health or physical hazard properties. These gases are not considered compressed until the pressure in their packaging exceeds 41 psia (282.5 kPa) at 68°F (20°C).

Computer Controlled System
Computer system plus its controlled function.

Computer Related System
Computerized system plus its operating environment.

Computer System
A group of hardware components and associated software designed and assembled to perform a specific function or group of functions.

Computerized System
A process or operation integrated with a computer system.

Concavity (welding)
A condition in which the surface of a welded joint is depressed relative to the surface of the tube or pipe. Concavity is measured as a maximum distance from the outside or the inside diameter surface of a welded joint along a line perpendicular to a line joining the weld toes.

Concentration Polarization
The phenomenon in ultrafiltration (UF) in which solutes form a dense, polarized layer next to the membrane surface eventually blocking further flow. UF systems counteract this by continuously flushing the solute away from the membrane surface.

Concurrent Process Validation
Establishing documented evidence that a process does what it purports to do based on information generated during actual implementation of the process.

Condensate
Distillate just after it has been cooled from steam into the liquid state.

Condenser
The heat exchanger used in distillation to cool steam in order to convert it from the vapor to the liquid state.

Conductivity
The reciprocal of resistivity (C=1/R). A measure of the ability to conduct an electric current. Since ionized impurities increase the conductivity of water, it is also an accurate measure of ionic purity. Conductivity is normally expressed in micromhos/cm (µmho/cm) or microsiemens/cm (µS/cm). To measure it, current is passed between two electrodes a fixed distance apart.

Configurable Software
Commercial, off-the-shelf software that can be configured to specific user applications without altering the basic program.

Configuration
The three-dimensional shape or form of a macromolecule.

Conformation
The characteristic three-dimensional shape (tertiary structure) of a macromolecule.

Conjugated Protein
A protein containing a metal or an organic prosthetic group or both. Hemoglobin is a conjugated protein.

Consent Decree
The result of a serious violation of federal regulations and related safety and quality standards. A company must agree to a series of measures aimed at bringing its manufacturing standards in compliance with federal regulations. Until agreed-upon conditions are met, a company may be forbidden to distribute its products in interstate commerce, except for those products deemed essential for the public health.

Conserved Sequence
A base sequence in a DNA molecule (or an amino acid sequence in a protein) that has remained essentially unchanged throughout evolution.

Containment
The action of confining within a defined space a microbiological agent or other entity that is being cultured, stored, manipulated, transported, or destroyed in order to prevent or limit its contact with people and/or the environment. Methods to achieve containment include physical and biological barriers and inactivation using physical or chemical means.

1. Primary Containment. Addresses the protection of personnel and the immediate laboratory environment from exposure to infectious agents. It involves the use of closed containers or safety biological cabinets along with secure operating procedures.

2. Secondary Containment. A system of containment that prevents the escape of infectious agents into the environment external to the laboratory. It involves the use of rooms with specially designed air handling, the existence of airlocks and/or sterilizers for the exit of materials and secure operating procedures. In many cases it may add to the effectiveness of primary containment.

1. Appendix G - Physical Containment specifies physical containment for standard laboratory experiments and defines Biosafety Level 1 (BL1) through Biosafety Level 4 (BL4). (also see: Biosafety Level, and Table II - Section II - Comparison of Good Large Scale Practice (GLSP) and Biosafety Level (BL) - Large Scale (LS) Practice)

2. Appendix I - Biological Containment specifies levels of biological containment (host vector systems) for prokaryotes and defines Host Vector 1 Systems (HV1) and Host Vector 2 Systems (HV2). (also see: Host Vector (HV) System)

3. Appendix K - Physical Containment for Large Scale Uses of Organisms Containing Recombinant DNA Molecules specifies physical containment guidelines for large scale (over 10 liters) research or production involving viable organisms containing recombinant DNA molecules, and defines GLSP (Good Large Scale Practice) through Biosafety Level 3-LS (Large Scale). (also see: Biosafety Level, and Table II - Section II - Comparison of Good Large Scale Practice (GLSP) and Biosafety Level (BL) - Large Scale (LS) Practice)

4. Appendix P - Physical and Biological Containment for Recombinant DNA Research Involving Plants specifies physical and biological containment conditions and practices suitable to the greenhouse conduct of experiments involving recombinant DNA-containing plants, plant-associated microorganisms, and small animals, and defines Biosafety Level 1-Plants (BL1-P) through Biosafety Level 4-Plants (BL4-P).

5. Appendix Q - Physical and Biological Containment for Recombinant DNA Research Involving Animals specifies containment and confinement practices for research involving whole animals, both those in which the animal's genome has been altered by stable introduction of recombinant DNA, and experiments involving viable recombinant DNA-modified microorganisms tested on whole animals, and defines Biosafety Level 1-Animals (BL1-N) through Biosafety Level 4-Animals (BL4-N).

Contaminant
Any unwanted or undesired component in a process fluid or controlled environment.

Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API (Active Pharmaceutical Ingredient) during production, sampling, packaging or repackaging, storage or transport.

Contig
Group of cloned (copied) pieces of DNA representing overlapping regions of a particular chromosome.

Contig Map
A map depicting the relative order of a linked library of small overlapping clones representing a complete chromosomal segment.

Continuous Fermentation
A process in which sterile medium is added without interruption to the fermentation system with a balancing withdrawal (or "harvesting") of broth for product extraction. The length of fermentation can be measured in weeks or months. Commercial applications of continuous fermentation are limited in number, with ethanol production by yeast the most important example.

Contract Manufacturer
A company holding an agreement requiring the performance of some aspect of API manufacturing

Control Area
A building or portion of a building within which the exempted amounts of hazardous materials may be stored, dispensed, handled, or used.

Control Group
The group of subjects in a controlled study that receives no treatment, receives a standard treatment, or receives a placebo.


Control Parameters
Those operating variables that can be assigned values and are used as control levels.

Control Serum
Serum used as a standard for clinical chemistry lab tests. Most often produced from outdated whole blood plasma. Most often turbid and difficult to filter

Controlled Area
An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination, and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure negative to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants.

Controlled Area
Area of restricted access. A term for areas and rooms adjoining a critical area in aseptic production facilities.

Conventional Drugs
New compounds made up by chemical synthesis or fermentation. These are termed by the FDA as NCEs (New Chemical Entities). The FDA rates conventional drugs with important therapeutic gain as 1-A drugs, for priority review. For example, AIDS drugs are conventional drugs approved for AIDS or AIDS-associated conditions.

Conventional Flow Cleanroom
A room supplied with filtered air with no specified requirement for uniform airflow patterns or velocity. Airflow patterns are usually turbulent.

Converted Data
Any original data that has been entered into a user-developed application (spreadsheet, database, report, etc.) for manipulation, evaluation, or review.

Convexity
A condition in which the surface of a welded joint is extended relative to the surface of the tube or pipe. Convexity is measured as a maximum distance from the outside or inside diameter surface of a welded joint along a line perpendicular to a line joining the weld toes.

Corn Steep Liquor
An ingredient in the culture medium for producing penicillin. A natural nitrogenous material that is a by-product of the corn milling industry.

Corrosive
A chemical that causes visible destruction or irreversible alterations in living tissue by chemical action at the site of contact. A chemical is considered corrosive if, when tested on the intact skin of albino rabbits by the method described in Appendix A of CFR 49 Part 173, it destroys or changes irreversibly the structure of the tissue at the site of contact following an exposure period of four hours. This term shall not refer to action on inanimate surfaces.

Corrosive Liquid
A liquid which when in contact with living tissue, will cause destruction or irreversible alteration of such tissue by chemical action. Examples include acidic, alkaline, or caustic materials.

Cosmid
Artificially constructed cloning vector containing the cos gene of phage lambda. Cosmids can be packaged in lambda p0hage particles for infection into E. coli: this permits cloning of larger DNA fragments (up to 45kb) that can be introduced into bacterial hosts in plasmid vectors.

CP (Cyclic Polarization)
An electrochemical test (ASTM G61) for metals that measures the point at which pitting corrosion begins. CP uses an electrolytic cell to directly measure the corrosion rate. By using the test piece as the working electrode, initiation of localized corrosion is shown by the potential at which the current density increases rapidly. This point is called the "pitting potential". The lower the current density at this point, the more resistance to pitting corrosion. The current density is measured in micro-amps per square centimeter.

Critical
A material, process step, or process condition, test requirement, or any other relevant parameter is considered critical when non-compliance with predetermined criteria directly influences the quality attributes of the API (Active Pharmaceutical Ingredient) in a detrimental manner.

Critical Area
An area where (sterile) product or contact surface is exposed, normally Class 100 (e.g., Point of Fill).

Critical Device
A device that directly ensures that a GMP Critical Parameter is maintained within predetermined limits (e.g., terminal HEPA filter, point of use filter). A malfunction of such a device would place product quality directly at risk.

Critical Instrument
An instrument that measures a GMP Critical Parameter, used to monitor and document that parameter.

Critical Parameter
A GMP or product quality parameter (e.g., differential pressure, unidirectional airflow pattern) that must be maintained within predefined limits to ensure product SISPQ (Strength, Identity, Safety, Purity, or Quality).

Critical Point
The combination of pressure and temperature at which the gas and liquid phases of a substance become indistinguishable.

Critical Process Step
For sterile products, this normally is an activity where product or product contact parts are exposed to the surrounding environment.

Critical Step(s)
The point or points in the process which, if not carried out properly or if contaminated, will not allow drug substances to be made such that they will meet their intended characterizations and impurity profiles.

Critical Surface
The part of the working surface to be protected from particulate contamination. It is within the Critical Zone.

Critical System
A structural, mechanical, or electrical system that can impact the processing parameters and attributes of the finished product or regulatory study. Critical systems may include utilities, process equipment, and systems.

Cross Contamination
The measurable and detrimental contamination of a material or product with another material or product.

Crossing Over
The breaking during meiosis of one maternal and one paternal chromosome, the exchanging of corresponding sections of DNA, and the rejoining of the chromosomes. This process can result in an exchange of alleles between chromosomes.

Cryogenic Liquid
A fluid that has a normal boiling point below -150°F (-101.1°C).

Cryptography
The mathematical science of deliberately scrambling and unscrambling information. Information is protected by being transformed (encrypted) into an unreadable format, called cipher text. Only those who posses a secret key can decypher (or decrypt) that message into plain text.

Culture Medium
Any nutrient system for the artificial cultivation of bacteria or other cells; usually a complex mixture of organic and inorganic materials.

current Good Manufacturing Practices (cGMP's)

Cut
An enzymatic break that occurs in both strands of a DNA molecule opposite one another by restriction enzymes.

Cystic Fibrosis
An inherited disease in which thick mucus clogs the lungs and blocks the ducts of the pancreas.

Cytokine
A protein that acts as a chemical messenger to stimulate cell migration, usually toward where the protein is released. Interlukins, lymphokines, and interferons are the most common.

Cytolysis
The dissolution of cells particularly by destruction of their cell membrane.

Cytopathic
Damaging to cells.

Cytoplasm
The protoplasmic contents of the cell outside the nucleus in which the cell's organelles are suspended.

Cytosine (C)
A pyrimidine occurring as a fundamental unit or base of nucleic acids.

Cytostatic Agents
Therapeutics that inhibit cell division and growth. This term can refer to machinery, such as those that would freeze cells.

Cytotoxic
Poisonous to cells.

Cytotoxicity
The ability of a substance or compound to cause a cytotoxic effect.