PDA Technical Glossary

Z-Value

The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat as the temperature changes during the heating and cooling phases of a sterilization cycle. (TR01) (TR3) The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat over time (i.e., calculation of F0) as the temperature changes in a cycle. (TR61)

Worst Case Soil

A soil that is the most difficult to clean from production equipment based on knowledge generated from laboratory studies, scientific properties, and/or production experience. (TR29)

Source: TR 29: Validation: Cleaning

Working Cell Bank (WCB)/Working Virus Bank (WVB)

A stock of cells or virus derived from the MCB/MVB and used to produce production cells, assay cells or virus production lots. (TR 47)

Biotechnology Validation Quality Risk Management/QRM Technology Transfer

Yield, Theoretical

The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production. (TR45)

Source: TR 45: Depth Filtration

GMP/Good Manufacturing Processes/cGMP Validation Quality Risk Management/QRM Technology Transfer

Worst Case

A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure. (TR60) A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure. (TR62) (TR60-2)

Source: TR 60: Process Validation

Worst Case Load

The load configuration that is determined to be most difficult to sterilize. This is a function of the cycle control strategy and load item characteristics (e.g., mass, configuration, or air removal challenges). For porous/hard goods loads, this may not necessarily be the minimum or maximum load. (TR01) The load configuration that is determined to be most difficult to sterilize or depyrogenate. This is a function of the process control strategy and load item characteristics (e.g., mass, configuration). (TR3)

Yield, Expected

The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale or manufacturing data. (TR45)

Source: TR 45: Depth Filtration

Virus (Relevant Virus)

A virus used in process evaluation studies that either is the virus, or of the same species as a virus known to or possible to contaminate the cell substrate or any other reagents or materials used in the production process. (TR47)

Virus Microbiology Validation

Temperature Probe/Sensor

A generic term used to describe any type of temperature measuring device that works through contact with the material or atmosphere to be measured. [Synonyms: Load Probe, Heat Penetration Probe, Temperature Distribution Probe, Drain Probe] (TR48)

Source: TR 48: Moist Heat Sterilizer Systems

Temperature Distribution

Temperature measurement of the heating medium (e.g., forced hot air) across the chamber load zone. (TR01) (TR03) (TR30) (TR48)

Manufacturing Filtration Validation

Throughput

The amount of solution that passes through a filter, described as volume per membrane area. [Synonym: capacity.] (TR15) The amount of solution that passes through a filter. It is described as volume through the membrane area. [Synonym: capacity] (TR26)

Source: TR 15: Validation: TFF in Biopharmaceuticals

Toxicity Studies (also referred to as “Tox” studies)

In vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions with the primary goals of identifying the following: 1) an initial safe dose and subsequent dose escalation schemes in humans; 2) potential target organs for toxicity and for the study of whether such toxicity is reversible; and, 3) safety parameters for clinical monitoring after the appropriate dosing and administering schedule is followed (relevant to the drug being studied). In toxicity studies, the test animals are examined by histological or serological methods in order to identify toxic, mutagenic, or teratogenic effects of the drug. It is sometimes possible to collect physiological data from the animals prior to sacrifice. Some toxicity studies may be performed using cell culture methods. Toxicity studies are also described by the U.S. FDA as “nonclinical laboratory studies” and by ICH as “preclinical safety evaluations”. The definition does not include studies using human subjects or clinical studies, field trials in animals, or any basic exploratory studies carried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics as described in ICH S6 and 21 CFR Part 58 (GLP). (TR56)

Source: TR 56: Phase Appropriate cGMP Application

Virus Biotechnology Validation Quality Risk Management/QRM

Tissue Culture Infectious Dose – TCID50

The dilution of virus that results in the probability of infection of 50% in replicate tissue-culture inoculations. (TR41)

Source: TR 41: Virus Filtration

Virus Biotechnology Microbiology Validation Quality Risk Management/QRM

Virus (Non-specific Model Virus)

A virus used for characterization of viral clearance of the process when the purpose is to characterize the capacity of the manufacturing process to remove and/or inactivate viruses in general, i.e., to characterize the robustness of the purification process. (TR47)

Virus Microbiology Validation

Transition Analysis

Mathematical evaluation of the chromatogram tracing as the mobile phase changes from one solution to another. An alternative to HETP and peak asymmetry for evaluating column packing and performance. (TR14)

Source: TR 14: Validation: Protein Purification Chromatography

Manufacturing Filtration Validation Technology Transfer

Transportation Study

Study performed to generate data to evaluate the effect of temperature variation on the product during transportation on product quality. Other test, such as vibration, pressure, and drop tests, may be considered. (TR39)

Source: TR 39: Cold Chain

Outsourcing Validation Quality Risk Management/QRM Supply Chain

Validation

A documented program that provides a high level of scientific assurance that a manufacturing process will reliably produce acceptable product. The proof of validation is obtained through rational experimental design and the evaluation of data, preferably beginning from the process development phase and continuing through the commercial production phase. (TR01) A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (TR26) (TR57) (TR70) (TR74) Documented testing, performed under highly controlled conditions, which demonstrates that a process consistently produces a result that meets predetermined acceptance a result that meets predetermined acceptance criteria. Used to test processes, methods, and systems for which conditions can be controlled in the real world (i.e., after completion of testing, when the process is in use). Transportation processes can be qualified but not validated; in the real world, it is not possible to exert control over all parameters that could affect the transportation process (e.g., weather, customs, traffic delays, mechanical failures, etc.). (TR58) A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (Note: Validation is a lifecycle program which may include development and qualification activities for one or more elements/systems that form a process.) (TR54-5) A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria (17). (TR60-3)

Validation Quality Risk Management/QRM

Validation

Use-related Risk Analysis

A systematic assessment of all of the user steps involved in using the device with particular consideration of the potential use errors, their associated clinical consequences along with the risk-mitigation strategies, and the method of validating the risk-mitigation strategies. (TR73)

Source: TR 73: Prefilled Syringe User Requirements for Biotech Applications

Test Article

Any food additive, color additive, drug, biologically derived product, etc., for human use or any other article subject to regulation. “Test Article,” in this report’s context, referring to the samples used for toxicity and stability studies. (TR56)

Source: TR 56: Phase Appropriate cGMP Application

Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Quality Risk Management/QRM Technology Transfer

Trend

A statistical term referring to the direction or rate of change of a variable(s) (ICH Q9). (TR54) (TR54-2)

Source: TR 54: QRM:Manufacturing Operations

Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Quality Risk Management/QRM

Thermometric Study

The utilization of independent temperature monitoring devices to determine a temperature profile within the load zone and analysis of the collected data. (TR3)

Source: TR 3: Validation: Dry Heat

Manufacturing Validation Quality Risk Management/QRM Sterile Processing

Validation, partial

A documented prospective study intended to demonstrate suitability for the intended use of previously validated methods, specifically for new products and/or processes. (TR57)

Validation

Thermocouple

A device for measuring temperature in which a pair of wires of different metals are joined and the free ends of the wires are connected to an instrument (such as a voltmeter) that measures the electrical potential difference created at the junction of the two metals. (TR3)

Source: TR 3: Validation: Dry Heat

Manufacturing Validation Quality Risk Management/QRM Sterile Processing

Transfer Disinfection

A disinfection process conducted on materials and equipment that coats the surface for a validated wetted time to remove bioburden prior to introducing such items into classified areas. (TR70)

Source: TR 70: Cleaning/Disinfection Programs

Targeted Species

The range of species for which detection or analysis is aimed for by an assay method. (TR50)

Source: TR 50: Alt. Methods Mycoplasma Testing

Microbiology Validation Quality Risk Management/QRM Sterile Processing

Target Criteria

Numerical limits, ranges, or other suitable measures of target performance levels of an analytical method that indicate suitable performance for intended use. For a method entering qualification, this is a target performance criterion that, when assessed, indicates that the method is qualified for its intended purpose. (TR57-2)

Source: TR 57-2: Analytical Method Development

Target Product Profile (TPP)

A format for a summary of a drug development program described in terms of labeling concepts to facilitate communication regarding a particular drug development program. (TR60) (TR60-2)

Source: TR 60: Process Validation

TCld50 Assay

Quantal assays for determining the titer of a virus. The 50% tissue culture infective does (TCID50) is the dilution of virus that results in the infection of 50% of cell cultures that have been infected with the same dilution of the virus sample. (TR47)

Virus Biotechnology Microbiology Validation Quality Risk Management/QRM Sterile Processing

Standard Deviation

<p>The statistical measure of the dispersion of the data. (TR57) </p>

Manufacturing Validation Quality Risk Management/QRM Technology Transfer

Specification

A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. (TR14) A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR38) (TR57) A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR69) A list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a drug substance, drug product, or materials at other stages of its manufacture should conform to be considered acceptable for its intended use. “Conformance to specification” means that the drug substance and drug product, when tested according to the listed analytical procedures, will meet the acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval. (TR56) (TR74) A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use (17). (TR60-3)(TR88)

Source: TR 14: Validation: Protein Purification Chromatography

Biotechnology Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Technology Transfer

Stakeholder(s)

Any individual, group or organization that can affect, be affected by or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, health-care professional, regulatory authority, and industry (ICH Q9). (TR54) (TR54-2) Any individual, group, or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. (TR54-5)

Source: TR 54: QRM:Manufacturing Operations

Outsourcing Validation Quality Risk Management/QRM Supply Chain Technology Transfer

Sporicidal Vapor Phase Decontamination

The destruction of inactivation of microbial spores using a vapor or gaseous agent. (TR51)

Source: TR 51: Biological Indicators

Manufacturing GMP/Good Manufacturing Processes/cGMP Microbiology Validation Quality Risk Management/QRM Sterile Processing

Site Acceptance Testing

The SAT is a series of tests that are performed as part of commissioning after the unit has been installed in the final location. (TR48)

Source: TR 48: Moist Heat Sterilizer Systems

Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Quality Risk Management/QRM Technology Transfer

Steam-in-Place (SIP)

The process of applying clean pressurized steam to a stationary piece of equipment in order to sterilize it. (TR41)

Source: TR 41: Virus Filtration

Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Sterile Processing

Spore Log Reduction (SLR)

The number of log reductions (10-fold changes) of spores from the initial population. For the overkill sterilization method, one targets a spore log reduction of 12 to achieve 1 x 10-6 probability of a survivor when using a biological indicator having a population of 1 x 106. (TR61)

Source: TR 61: Steam in Place

Manufacturing GMP/Good Manufacturing Processes/cGMP Microbiology Validation Quality Risk Management/QRM Sterile Processing

Signal Detection Theory

A means to quantify the ability to discern between signal and noise. According to the theory, there are a number of determiners of how a detecting system will detect a signal, and where its threshold levels will be. The theory can explain how changing the threshold will affect the ability to discern, often exposing how adapted the system is to the task, purpose or goal at which it is aimed. (TR55)

Source: TR 55: TBA/TCA Detection Mitigation

Validation Technology Transfer

State of Control

A condition in which the set of controls consistently provides assurance of continued process performance and product quality. (TR57)

Manufacturing Validation Quality Risk Management/QRM Technology Transfer

Specific Model Virus

Virus that is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties as those of the observed or suspected virus. (TR41)

Source: TR 41: Virus Filtration

Virus Validation Quality Risk Management/QRM Technology Transfer

Stability Profile

The physical, chemical, biological, and microbiological behavior of a drug substance or drug product as a function of time when stored under the defined environmental conditions of an approved protocol. (TR39)

Source: TR 39: Cold Chain

Manufacturing Validation Quality Risk Management/QRM Technology Transfer

Spiking

The addition of a small known amount of a known compound to a standard, sample, or placebo, typically for the purpose of confirming the performance of an analytical procedure or the calibration of an instrument. (TR57)

Manufacturing Validation Quality Risk Management/QRM

Sporicide

A compound that destroys all vegetative microorganisms and bacterial and fungal spores. (TR70)

Source: TR 70: Cleaning/Disinfection Programs

Manufacturing GMP/Good Manufacturing Processes/cGMP Microbiology Validation Quality Risk Management/QRM Sterile Processing

Specificity

The ability of an analytical procedure to accurately measure or detect a target analyte in the presence of other components in the sample matrix. (TR50) The ability to assess unequivocally the analyte in the presence of components that may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). (TR57) The ability to detect a range of microorganisms, which demonstrate that the method is fit for its intended use. (TR33)

Source: TR 33: Rapid Micro Methods

Biotechnology Manufacturing GMP/Good Manufacturing Processes/cGMP Validation Technology Transfer

Significant Body of Information

A significant body of information on the stability of the drug product is likely to exist after 5 years of commercial experience for new molecular entities, or 3 years of commercial experience for new dosage forms (TR38)

Source: TR 38: Manufacturing Chromatography Systems Postapproval Changes (ChromPAC)

Inspections Outsourcing Validation Quality Risk Management/QRM

Stability-Indicating Analytical Method

A test procedure that is able to discern changes in an analyte due to degradation processes. It is capable of accurately measuring changes in the product that can occur under conditions of physical or chemical stress. (TR57)

Manufacturing Validation Quality Risk Management/QRM Technology Transfer

Standard Pressure

A pressure of 1 atmosphere (14.70 psi or 760 mm of mercury) to which measurements of quantities dependent on pressure are often referred. (TR45)

Source: TR 45: Depth Filtration