PDA Technical Glossary

An input process parameter that should be controlled within a meaningful, narrow operating range to ensure that API quality attributes meet their specifications. Although parameters with wide operating ranges may also impact product quality, they are generally easily controlled and not as likely to result in excursions that affect quality and are therefore low risk. [Synonym: critical process parameter (CPP)] (TR14)

A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (TR60) A process parameter whose variability has an impact on critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (TR74)

An input process parameter that should be carefully controlled within a narrow range and is essential for process performance. A key operational parameter does not affect critical product quality attributes. If the acceptable range is exceeded it may affect the process (e.g., yield, duration) but not product quality. (TR14)

An input process parameter that should be carefully controlled within a narrow range and is essential for process performance. A key process parameter does not affect product quality attributes. If the acceptable range is exceeded, it may affect the process (e.g. yield, duration) but not product quality. (TR60)

An input variable or condition of the manufacturing process that can be directly controlled in the process. Typically, these parameters are physical or chemical (e.g., temperature, process time, column flow rate, column wash volume, reagent concentration, or buffer pH). [Synonym: process parameter] (TR14)

An output variable or outcome that cannot be directly controlled but is an indicator that the process performed as expected. [Synonym: performance attributes] (TR14)

An input variable or condition of the manufacturing process that can be directly controlled in the process. Typically, these parameters are physical or chemical (e.g. temperature, process time, column flow rate, column wash volume, reagent concentration, or buffer pH). (TR60)

Process used to by a chromatographic system to determine the peak area (based on height and width) and obtain the quantitation of the peak of interest. The measurement is based on the integral technique of splitting the peak into a large number of rectangles, which are then summed to provide an estimate of the total area under the peak. (TR80)

An output variable or outcome that cannot be directly controlled but is a measurable indicator that the process performed as expected (e.g., bioburden, load monitor). [Synonym: performance parameter] (TR30)

Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications. (TR3) (TR14) (TR45) (TR42) (TR48) (TR61) (TR64) Transport tests of product or representative product that is conducted during actual transportation or distribution. (TR39) Documented evidence that provides a high de­gree of assurance that the equipment and/or system functions accurately and consistently according to predetermined specifications in its operating environment. (TR54-5) Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications (17). (TR60-3)

A technique widely used in molecular biology in which a DNA polymerase is used to amplify a piece of DNA by in vitro enzymatic replication. As PCR progresses, the DNA thus generated is itself used as a template for replication. This sets in motion a chain reaction in which the DNA template is exponentially amplified. This technique may be used to quantify virus. (TR41) (TR47)

The degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of the same suspension of microorganisms and using different suspensions across the range of the test. Also known as repeatability. (TR33) The closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision, and reproducibility. It is usually expressed as the variance, standard deviation, or coefficient of variation of a series of measurements. (TR57)

The closeness of agreement between a series of measurements obtained within laboratory variations (e.g., different days, different analysts, different equipment). (TR57)

The closeness of agreement between a series of measurements for the same sample obtained among different laboratories. (TR57)

An unanticipated rapid increase in fluid flow. [Synonym: Hydraulic Shock] (TR45)

Rapid backward fluid flow that may result in filter rupture. (TR45)

Rapid increase in forward fluid flow that may dislodge particulates. (TR45)

A short synthetic single-stranded nucleic acid complementary to a specific sequence of a target gene, DNA or RNA. It usually serves to initiate the de novo synthesis of nucleic acid from a template. (TR50)

A series of operations and/or actions used to produce a desired result. (TR38)

A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. (TR60) (TR60-2)

Studies performed during process development to establish acceptable ranges for key input vari­ables and critical operational parameters that de­fine the process design space. (TR56) A study that evaluates the process to increase process knowledge and examines proposed ranges and their individual and/or combined impact on target protein quality. Process characterization studies include deliberate variation of parameters to determine their effect on product quality attributes, often conducted as small-scale studies. (Also known as process evaluation studies, process justification studies, engineering studies, development studies, robustness studies, or process design studies. (TR60)

Viral clearance studies in which nonspecific model viruses are used to assess the general virus clearance capacity of the manufacturing process to remove and/or inactivate viruses. (TR41)

Viral clearance studies in which relevant and/or specific “model” viruses are used to determine the ability of the manufacturing process to remove and/or inactivate these viruses. (TR41)

A document, typically prepared by R&D, that describes the intended manufacturing process. The PFD includes all relevant information for the operation of the manufacturing process, organized by unit operation. The PFD serves as the source document for the initial development of the master production records and is locked down once development has determined that the process can be controlled. (TR65)

Documented verification that a system is capable of consistently performing or controlling the activities of the processes it is required to perform or control, according to written and preapproved specifications, while operating in its specified operating environment. (TR01)

Documented verification that a system is capable of consistently performing or controlling the activities of the processes it is required to perform or control, according to written and preapproved specifications, while operating in its specified operating environment. (TR3) Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. (TR54) (TR60) (TR54-5)

Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality. (TR60)

Method of evaluating an aseptic process using a microbial growth medium employing methods which closely approximate those used for sterile materials. (TR28)

Method of evaluating an aseptic process employing methods which closely approximate those used for sterile materials using an appropriate material. (TR28)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API (drug substance) meeting its predetermined specifications and quality attributes. (TR14) (TR42) Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. (TR44) The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. (TR54) (TR57) (TR74) The collection and evaluation of data, from the pro­cess design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product. The documented evidence that the process, op­erated within established parameters, can per­form effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes, as described in EMA, EU GMP, Part 1, Annex 15, drug/me­dicinal product. (TR56) EMA: The documented evidence that the process, op­erated within established parameters, can per­form effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. US FDA: The collection and evaluation of data, from the process design stage through commercial pro­duction, which establishes scientific evidence that a process is capable of consistently deliver­ing quality products. (TR60-2) The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or drug substance meeting its predetermined specifications and quality attributes (1, 17). (TR60-3)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. (TR60) (TR54-5)

A document that defines the process validation scope and rationale and that contains the list of process validation studies to be performed (Synonym: Validation Master Plan). (TR42) (TR60) The plan that documents rationale for the approach to validation and lists all systems and their validation status. (Note: The VMP can be used to document the rationale for number of monitors and revalidation frequency, as well as other system justifications). (TR52)

A written plan pre-approved by the quality unit that specifies critical steps, controls, and measurements. The process validation protocol states how validation will be conducted, identifying sampling, assays, specific acceptance criteria, production equipment, and operating ranges. Results obtained for each study described in the protocol should be evaluated in an associated process Validation report. (TR14) (TR42)

A report approved by the quality unit that summarizes specific tests performed, compares the test results with the protocol acceptance criteria, and addresses deviations encountered during the study. (TR14) (TR42)

The duration of time for a phase of a manufacturing unit operation or the entire operation. (TR41)

Procedural steps taken for switching from the manufacturing of one product to another product. (TR29)

All phases in the life of a product from the initial development through marketing until the product’s discontinuation (ICH Q8[R2]. (TR54) (TR54-5)

A predefined, written procedural method for the design and implementation of experiments to define and document the methodology and criteria required to assess the capability of a temperature-controlled system to achieve the desired result. (TR64)

A deviation that occurs when a result is unexpected (i.e., fails to meet the predetermined acceptance criteria) or a procedure in the protocol cannot be executed as written (e.g., when a challenge is conducted using a methodology other than that described in the protocol or a process/ piece of test equipment fails). (TR64)

A report generated at the completion of the activities identified in an individual validation protocol that summarizes deviations and conclusions. (TR64)