PDA Glossary

Generally used to indicate Phase 1 and A clinical studies.(TR 56)

Generally used to indicate the following clinical study activities: Microdosing Studies, Phase 1 Trials, Phase 2 Trials, and Phase 3 Trials. See any of the following studies for more information. (TR56)

Studies designed to speed up the development of promising drugs by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. May include the administration of single sub therapeutic doses of the study drug to a small number of subjects (10 to 15) to gather preliminary data on the agent’s pharmacokinetics (how the body processes the drug) and pharmacodynamics (how the drug works in the body). A microdosing study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. (TR56)

Phase 1 trials are the first stage of testing in human subjects. Often, a small (20-100) group of healthy volunteers will be selected. For life-threatening indications such as oncology, these can be patients that have the target disease but may not yet be the ideal target population. This Phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. (TR56)

Once the initial safety of the study drug has been confirmed in Phase 1 trials, Phase 2 trials are performed on larger groups (20-300) are designed to assess efficacy, as well as to continue safety assessments in a large group of volunteers and patients. Phase 2a is specifically designed to assess dosing requirements (how much drug should be given). Phase 2b trials are specifically designed to study efficacy (how well the drug works at the prescribed dose(s). (TR56)

Final clinical stage Phase 3 trials are designed to demonstrate the potential advantages of the new therapy over other therapies already on the market; safety and efficacy of the new therapy are studies over a long period of time and many more patients (1,000-3,000) are enrolled into the study with less restrictive eligibility criteria; phase 3 studies are intended to help scientists identify rarer side effects of treatment and prepare for a broader application of the product; phase 3 trials enroll patients to verify efficacy and monitor adverse reactions during longer-term use. (TR56)

The fraudulent, intentional substitution or addition of a substance in a product for the purpose of increasing the apparent value of the product or reducing the cost of its production (i.e., for economic gain). (TR54-3)

A device that produces vacuum by means of the Venturi effect. [Synonym: Aspirator, ejector pump] (TR48)

The total surface area of the filter available to the process fluid. (TR26)

The liquid flowing out of a column. (TR14)

Fluid that flows out of a process step. (TR26)

Thermoplastic material formulation (that may or may not contain rubber/natural latex) derived from elastic polymer; often used interchangeably with the term “rubber.” (TR73)

An array of electronic sensors designed to selectively identify chemicals responsible for odors. The zNose™ system is one example that is commercially available and consists of a vapor pre-concentrator, a direct-heated high-speed chromatography column, a solid-state sensor and a programmable gate array microprocessor system. (TR55)

A record used for GMP purposes or for regulatory submission that is stored electronically for the purposes of reproduction, retrieval or archival. (TR48)

Solution (effluent) that flows out of the chromatographic column containing the drug substance. [Synonym: collected product fractions] (TR14)

Desorption of a drug substance from a chromatographic column. (TR14)

The emissivity of the surface of a material is its effectiveness in emitting energy as thermal radiation. This is measured between 0 (zero) and 1 (one); 0 having the ability to reflect all energy, and 1 allowing all energy to pass through it. Glass, for example, has emissivity of 0.91 (smooth, uncoated); aluminium foil has emissivity of 0.03. (TR72)

A dispersed colloidal system consisting of two immiscible liquid phases generally stabilized with one or more suitable agents. Injectable emulsions are sterile liquid dosage forms of drug substances dissolved or dispersed in a suitable emulsion me­dium. Injectable emulsions are for parenteral ad­ministration of poorly water-soluble drugs. (TR79)

A tool or process which provides the means to achieve an objective (ICH Q10). (TR54)

Cells cultured (under conditions comparable to those used in production) from the MCB or WCB to a passage level or population doubling level comparable to or beyond the highest level reached in production. Note: The ICH term is: “Cells at Limit of invitro Cell Age Used for Production”.
Note: The term as defined in ICH Guidance Q5 D is “Cells at Limit of in vitro Cell Age Used for Production”; also abbreviated as EPC. (TR56)

A virus that pre-exists in the genome of the cell substrate. (TR71)

A virus that integrates into the genome of the cell substrate. (TR83)

Virus-like entity whose genetic material is stably integrated into the germ line of an organism or cell line. Cell lines (notably CHO) may constitutively produce virus-like particles, which are typically noninfectious but still of safety concern. Model retroviruses are generally used as surrogates to measure virus-like particle clearance. (TR41)

A type of spore formed intracellularly by some bacterial genera. (TR51)

An article challenged with a vial of endotoxin (or a carrier spiked with endotoxin) designed for use in depyrogenation studies. The endotoxin (a purified lipopolysaccaride) is validated for use in or on an endotoxin indicator. The carrier is made from a material appropriate for the intended depyrogenation processes to which it will be subjected. The endotoxin on a carrier is added at a concentration sufficient to allow recovery of a minimum of 1000 USP endotoxin units/carrier. The endotoxin indicator would allow for accurate indication of at least a 3-log reduction in USP endotoxin units during depyrogenation process challenges. (TR3)

A classical PCR method based on repeated cycling of the reaction mixture between two or three temperatures (denaturing, annealing, and extension) with detection of the amplified product after reaction completion (e.g., by agarose gel electrophoresis). (TR50)

Conditions and corresponding measurements as associated with facilities and equipment used in the control of a manufacturing area that may impact the identity, strength, quality, or purity of a product. Among such parameters are airflow rates and patterns, pressure differentials, materials and personnel flow, temperature and relative humidity, as well as nonviable and viable particulates. (TR13)

Microorganisms associated with a processing environment. (TR22)

Describes the processes and activities that need to take place to characterize and monitor the quality of the environment. (TR70)

Monitoring for nonviable particulates and/or microorganisms where the result meets or exceeds the alert and/or action level or limit. (TR88)

Defined documented program which describes the routine particulate and microbiological monitoring of processing and manufacturing areas, and includes a corrective action plan when action levels are exceeded. It includes assessment of environmental air, surfaces and personnel. (TR22) (TR28) (TR62)

A biochemical technique used to detect or measure the presence of an antibody or an antigen in a sample. (TR41) (TR47)

Column washing with a solution or buffer(s) in preparation for the column load. (TR14)

The period that elapses between the attainment of the minimum exposure temperature at the reference measurement point (typically the drain) and the attainment of the sterilization temperature at all points within the load. This period is an indication of the ability to properly remove air and heat the load items; consequently, it is typically only evaluated by placing heat penetration probes in porous/hard goods loads. (TR01) (TR48)

The moisture content of wood below the fiber saturation point is a function of both the relative humidity and the temperature of surrounding air. The equilibrium moisture content (EMC) is the moisture content at which the wood is neither gaining nor losing moisture; this however, is a dynamic equilibrium and changes with relative humidity and temperature. (TR55)

Automated or non-automated, mechanical or non-mechanical equipment used to produce the drug product, including equipment used to package the drug product. (TR38)

The sequence of equipment through which a product is produced or processed. (TR29) (TR49)

See Comparability. (TR38)

A comparison with the primary objective of showing that the results from two methods differ by an amount which has negligible impact on fitness for use. This is usually demonstrated by showing that the true difference is likely to lie between a lower and an upper equivalence margin of acceptance differences. (TR57)

The largest difference between the results from two methods that is considered as being scientifically and statistically acceptable. (TR57)

Test of conformance to interval-based target acceptance criteria; differs from most common statistical tests in the nature of the statistical hypothesis. In equivalence testing, the alternative hypothesis is that the difference is sufficiently small that no important difference exists. A common statistical procedure used for equivalence testing is the two one-sided T-test. (TR57-2)

A measure of how similar the test results are when compared with the existing method. (TR33)

Deviation from expected value. Error may be random or systematic. (TR57)

A self-evident documented mistake that will bring the validity of a laboratory test into question. (TR88)

A self-evident documented mistake that will bring the manufacturing process into question. (TR88)

Component that transfers heat out of or into the CES (to control the area temperature). (TR64)

A systematic technique that employs forward logic to construct a graphical representation of consequences from an initiating event. (TR54)

A component of a drug formulation that has no active pharmacologic function. Excipients are commonly used in drug formulations as modulators of pH or osmolality for parenteral administration and as stabilizers for APIs. (TR54-4)

An ingredient added intentionally to the drug substance that should not have pharmacological properties in the quantity used. (TR57)

Inactive pharmaceutical ingredients in a product formulation that are responsible for the product’s manufacturability and physicochemical attributes. (TR67) (TR88)

The capacity of an assay not to detect microorganisms closely related to a target microorganism. (TR33)

A temperature or humidity deviation from conditions such as those specified by product labeling or shipping specifications. (TR53)

Measurement that exceeds an alert, concern, or action level/limit by either a discreet value or an increasing/decreasing trend. (TR69)

Lipopolysaccharides from the cell walls of bacteria, the most potent of which derive from Gram-negative organisms. When injected, they are known to cause a febrile, or fever-producing reaction that can cause severe patient reactions, and on occasion, can be fatal. (TR26) (TR44)

Pyrogenic lipopolysaccharide component of Gram-negative bacterial cell walls.(TR69)

The major constituent of the outer membrane of Gram-negative bacteria is composed of lipid A, the core polysaccharide, and the O-antigen polysaccharide; endotoxin is also known as lipopolysaccharide (LPS).(TR82)

The phase of the sterilization cycle in which the appropriate parameters are maintained within defined ranges for the time (exposure time or dwell period) and temperature determined to be necessary to achieve the desired lethality. (TR1) (TR3) (TR30) (TR48) (TR61)

A type of compounding whereby a drug or combination of drugs and/or excipients is prepared under the supervision of a pharmacist to create a customized medication dosage form in accordance with a clinical protocol. (TR63)

Refers to a legislative requirement that packaging manufacturers “take back” their packaging, or otherwise ensure (through a tax) that it is collected and properly disposed of. (TR46)

Product of microbial growth, particularly in biofilms, composed of polysaccharides, lipids, proteins, and nucleic acids; produced by bacteria and fungi; is an important mediator of microbial attachment to surfaces and biofilm formation. (TR69)

A chemical component that is removed from a material by application of an artificial or exaggerated force (e.g., solvent, temperature, time). The term extractable is often erroneously used to describe a leachable. (TR14) (TR15) (TR26) (TR41) (TR45)

Chemical substances that can be extracted from components of material process fluid contact surfaces by exertion of an exaggerated force (e.g., organic solvent, extreme elevated temperature, ionic strength, pH, contact time, etc.) Extractables may represent most but not all of the potential leachables that may be seen in process fluids. (TR66)

Extractables are organic and inorganic chemical entities that can be released from a pharmaceutical packaging/delivery system, packaging component, or packaging material of construction under laboratory conditions. (TR54-4)

Organic or inorganic chemical entity that is forced out of container closure system materials and components under laboratory experimental conditions. (TR73)

A known test article processed with a nucleic acid extraction procedure in order to ensure the proper extraction of nucleic acid. (TR50)

The efficiency of extraction of target analyte from a test matrix. It is usually measured as ratio (percentage) of analyte amount extracted from the matrix to that originally present in the matrix before extraction. (TR50)

Those particles that are not part of the formulation, package, or assembly process but rather are foreign and unexpected. Materials such as rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a product-contact material. (TR78)

Foreign material that comes from outside the primary process.  Often these are from the manufacturing environment or incomplete cleaning of components. They are uncontrolled. (TR85)

Filled syringe delivery force (that does not include break-loose force) quantified as the highest non-break-loose force to complete the injection stroke. (TR73)