PDA Technical Glossary

Procurement of a product such as liquid or powder format culture media or buffer and that has been supplied in single-use technology. (TR66)

A sterility release system based upon effective control, monitoring, documentation, and batch records review of a validated sterilization process cycle in lieu of release procedures based upon end-product sterility testing. (TR01) (TR3) (TR13) A sterility release program based on effective control, monitoring and documentation of a validated sterile-product manufacturing process where sterility release is based on demonstrated achievement of critical operational parameters and performance attributes in lieu of end-product sterility testing. (TR30)

The “tube” of polymer extruded by the BFS machine from which the containers are formed. (TR77)

Any microorganism which by direct interaction with (i.e., infection of) another organism causes disease in the organism (by convention, a multi-cellular organism). (TR51)

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)

Re-execution of qualification studies performed on a periodic basis to verify that systems and pro­cesses remain able to produce a result that con­sistently meets predetermined acceptance criteria through execution of a lab or field study. (TR54-5)

A licensed pharmacist who is assigned the responsibility and authority for establishing and implementing policies and procedures for all operations of the pharmacy and to ensure the pharmacy operations and practices comply with all requirements of national and local pharmacy and drug laws, rules, and regulations. (TR63)

Utilities include pharmaceutical-grade water systems, compressed gases, pharmaceutical-grade air systems, heating, ventilation and air conditioning systems, and space pressurization. (TR67)

A test article used to assess the performance of an assay in the known presence of a targeted microorganism or nucleic acid. A positive control is used to monitor the performance of assay routinely and during validation. For culture-based assays, a live mycoplasma preparation must be used to show that the assay was run properly. NAT positive controls use a nucleic acid with the target sequence of interest. (TR50)

Unit filled in an aseptic processing simulation that exhibits detectable microbial growth after incubation. (TR22) (TR62)

Inspection of glass containers after product filling. (TR43)

A tool of analysis based on applying prior experience or knowledge of a hazard or failure to identify future hazards, hazardous situations and events that might cause harm, as well as to estimate their probability of occurrence for a given activity, facility, product or system. (TR54-5)

Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. NOTE: Preventative action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. (TR54)

All process surfaces that have a direct influence on the quality of the drug substance being manufactured, including surfaces processing equipment, storage containers, and of processing aids during manufacturing operations. (TR54-4)

The number that expresses the probability of occurrence of a non-sterile unit after exposure to a sterilization process. Within the pharmaceutical industry, a design end point better than or equal to the probability of one non-sterile unit in a million units is expected, i.e., PNSU ≤ 10–6. [Synonym: Steriliy Assurance Level (SAL)] (TR01)

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)

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 microorganism that can adversely affect the appearance, physicochemical attributes or therapeutic effect of a nonsterile product. (TR67)

The process flow in which a product is manufactured.(TR43) The process flow in which a product is manufactured that is often described in a process map.(TR 76)

A sterilization design approach that is based on the characteristics of the bioburden (on or in the load) and the heat sensitivity of the product that delivers the lethality needed to achieve a PNSU of 10-6 on or in the items to be sterilized. (TR01) (TR3) (TR30)

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)

Any substance capable of eliciting a febrile (or fever) response upon injection or infection (as in endotoxin released in vivo by Gram-negative bacteria. (TR3) Fever-producing substance (TR69) A material that elicits a pyrogenic response (fever). (TR70)