PDA Technical Glossary

Numerical limits, ranges, or other suitable measures for acceptance of test results. (TR 14) (TR 29) (TR 38) (TR 64) Numerical limits, ranges, or other suitable measures for acceptance of test results. Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation. Exceeding the operating range should be documented and explained in the validation report and evaluated for validation study impact. (TR 42) The pre-defined specifications, standards or ranges that must be met under stated test conditions. (TR 48) Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical method validation that is satisfied to determine suitability of test method performance.(TR 57) (TR 69) (TR 72) (TR 74) The criteria that a system or component must satisfy in order to be accepted by a user or other authorized entity. (TR 54-5) Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures which the drug substance or drug product or materials at other stages of their manufacture should meet (16). Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation and possible batch rejection. (TR60)

A physical, chemical, or microbiological property or characteristic of an input or output material. (TR60)

An output variable or outcome that cannot be directly controlled, but is an indicator that the process performed as expected.(Synonym - Process Performance Parameter) (TR60)

A molecular or product characteristic that is selected for its ability to indicate the quality of the product. Collectively, the quality attributes define identity, purity, potency and stability of the product, and safety with respect to adventitious agents. Specifications measure a selected subset of the quality attributes. (TR60)

Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not intended to be part of the manufacturing process of the drug substance or drug product (16). The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API [drug substance] during production [manufacture], sampling, packaging or repackaging, storage or transport (17).

Assuring that during routine production the process remains in a state of control. (TR60) US FDA: Assuring that during routine production the process remains in a state of control. ICH: An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (TR60-2)

At least two process unit operations conducted under predetermined control conditions without process interruptions, where real-time process controls (PATs) may be used to meet the process requirements.

An alternative approach to process Validation in which manufacturing process performance is continuously monitored and evaluated. (TR60)

Following comprehensive assessments of scientific evidence and risk, quality attributes are ranked according to the degree of criticality. The continuum, as opposed to binary classifications of Critical and Non-Critical, is thought to “more accurately reflect complexity of structure-function relationships and the reality that there is some uncertainty around attribute classification”. (TR60)

A non-discrete scale where parameters or attributes are evaluated relative to their impact on drug substance and drug product quality. (TR60)

A planned set of controls, derived from current product and process understanding, which ensures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. (TR 54) (TR 60) (TR 54-5) (TR56)

The multidimensional combination and interaction of input variables (e.g., material attributes) and operational parameters that have been demonstrated demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (TR30) (TR60) (TR 57-2)

A method for carrying out carefully planned experiments on a process. Usually, DoE involves a series of experiments that initially involves evaluating many variables and then focuses on a few critical ones. (TR54-4) A structured, organized method for determining the relationship between factors affecting an assay and output of that assay. (TR57) (TR57-2) (TR74) A structured, organized method for determining the relationship between factors affecting a process and the output of that process (8). (TR60)

Documentation and description of work done during the early phases of development. The goal is to document information about the way the process works and to document why key choices were made in selecting the specifics of the process (e.g., flow rate or temperature). These documents can serve as a reference during investigations of discrepancies and during the design of specific Validation and characterization studies.(TR14) (TR 42) Documentation and description of work done during the early phases of development (Stage 1). The goal is to document information about the way the process works and to document why key choices were made in selecting the specifics of the process (e.g., flow rate or temperature). These documents can serve as a reference during investigations of deviations and during the design of specific validation and process characterization studies.(TR60)

A pharmaceutical product type that contains a drug substance, generally, in association with excipients. [Synonym: Dosage Form; Finished Product] (TR57)(TR14)(TR42) A finished dosage form (e.g., tablet, capsule, or solution) that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.(TR38) (TR67) (TR88) The dosage form in the final immediate packaging intended for marketing.(TR60)(TR82)

The active ingredient that is subsequently formulated with excipients to produce the drug product. It can be composed of the desired product, product-related substances, and product- and process-related impurities. It may also contain excipients, including buffers and other components. [Synonyms: bulk drug substance, bulk material, active pharmaceutical ingredient (API)] (TR14) (TR57) (TR74) (TR60) Active pharmaceutical ingredient in a drug product that is responsible for that product’s therapeutic activity.(TR67) (TR82) (TR88) See Active Pharmaceutical Ingredient (API). (TR56)

A structured, organized method for determining the relationship between factors affecting a process and the output of that process. (TR60)

Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements. (TR14) (TR42) (TR48) (TR61) (TR64) The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manu­facturer’s recommendations. (TR54-5) Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements (17). (TR60)

A material produced during the steps of the processing of an API that undergo further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (TR60)

All phases in the life of a product from the initial development through marketing until the product’s discontinuation. (TR54) (TR60) All phases in the life of a product, from the initial development through marketing until the prod­uct is discontinued. (TR60-2)

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 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). (TR60)

Development of a production strategy for a new drug starting from manufacturing processes similar to those used to manufacture other drugs of the same type (the production for which there already exists considerable experience). (TR60)

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)

A written plan preapproved by the quality unit that specifies critical steps, controls, and measurements. The process performance qualification protocol states how process performance qualification or other validation studies 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. (TR60)

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)

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 prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product. (TR60) (TR54-4)(TR 81)(T60-3)

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)

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)