PDA Technical Glossary

Step in a chromatography cycle designed to flush the column to remove substances acquired during a previous step (often used between the load and elution steps). (TR14)

A discrete step or manipulation in a manufacturing process where process and operating parameters are defined to achieve a specific process objective. [Synonym: process step] (TR74)(TR14)

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)

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)

To mix resin particles in a liquid to achieve a homogenous liquid suspension. (TR14)

A homogenous distribution of resin particles in a liquid. (TR14)

A solution typically selected to control bioburden during column storage. (TR14)

Repeating partial or full validation of a process after a process change is implemented. Re-validation is change-based, not time-based. (TR14) (TR3) (TR42)

Validation of an existing manufacturing process that occurs by reviewing data from relevant historical and test production records. (TR14) (TR42)

A small-scale process step that has been demonstrated to be representative of a production-scale operation. (TR14)

Reduction of microbial contaminants to safe levels as judged by public health requirements for the specific country. (TR13) A significant reduction in bioburden, achieved in chromatography by the use of bactericidal agents, such as sodium hydroxide (NaOH), hydrochloric acid (HCl), ethanol (EtOH), and isopropanol (IPA). (TR14) The process of reducing microbial levels by treatment at less than defined sterilizing conditions. Typically water at 80 °C or a chemical treatment is used to perform sanitization of process components. (TR45) A process that reduces the number of viable microorganisms to a defined level. (TR61) (TR69)

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)

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)

Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR14) (TR61) (TR64) (TR72) The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR54-5) Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges (17). (TR60-3)

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)

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

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)

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 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)

A chemical component that migrates from a contact surface into a drug product or process fluid during storage or normal use conditions. The term leachable is often erroneously used to describe an extractable. (TR14) (TR26) Leachables are organic and inorganic chemical entities that migrate from a packaging/delivery system, packaging component, or packaging material of construction into an associated drug product under normal conditions of storage and use or during accelerated drug product stability studies. Leachables are typically a subset of extractables or are derived from extractables. (TR54-4) Chemical substances that are leached, from product-contact or non-product-contact materials, under typical process conditions and detected in final dosage. Leachables may be a subset of extractables, and can include their reaction or breakdown products. (TR66) Organic or inorganic chemical entity that migrates from pharmaceutical container closure system components into a drug product formulation. (TR73)

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 measurement of column packing efficiency or integrity, calculated from the column height divided by the number of theoretical plates. (TR14)

Any component present in the drug substance or drug product that is not the desired product, a product-related substance, or excipient including buffer components. It may be either processor product-related. (TR14) (TR57) (TR74) Any component present in the drug substance or drug product which is not the desired product, a product-related substance, or excipient. It may be either process- or product-related (17). (TR60)

A porous sieve or screen installed at the top and bottom of a column used to retain chromatography resin particles and allow passage of the process stream. [Synonym: sinter] (TR14)

Effluent that may contain the product that is not retained by chromatography resin during column loading. (TR14)

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)

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

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)

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

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)

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)

Any adventitiously or externally introduced material(s) (e.g., chemical, biochemical, or microbial species) not intended to be part of the process. (TR14) (TR15) (TR70) An undesired impurity of a chemical or microbiological nature that is introduced into a raw material, intermediate, or API (drug substance) during manufacture. (TR14) (TR15) 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. (TR69) (TR74) Any adventitiously introduced material (e.g., chemi­cal, biochemical) or microorganisms including viruses not intended to be included in the manufacturing process of the drug substance or drug product. (TR83)

A pre-determined number of production lots, typically three, that represent the process and are evaluated to demonstrate consistency. [Synonyms: validation, consistency, demonstration lots, qualification lots] (TR14) (TR42)

The solute that is passed through the column for separation. (TR14)

Preparation of a column that includes the addition of resin slurry into a column to create a bed suitable for its intended use. Characteristics of a packed column bed include bed height and diameter, backpressure, and number of theoretical plates. (TR14)

Data recorded during performance of a chromatography unit operation typically includes UV absorption (280 nm), pH, and conductivity, as well as other data (e.g., flow rates or pressure). (TR14)

A series of tests designed to increase process knowledge by examining proposed operational ranges and their individual and/or combined impact on the chromatography process. (TR14) A late-stage study that evaluates the process to increase process knowledge and examines proposed operational ranges and their individual and/or combined impact on target protein quality. (TR42)

Synonym: Drug Substance. (TR14) (TR42) A substance or mixture of substances that, when delivered in a finished drug product, directly affects the structure or function of the body. (TR54-4) Any substance or mixture of substance intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. Note: also known as Drug Substance. (TR29) (TR56) (TR41) (TR54-3) (TR60) Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity o other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. (TR63) (TR70) Any substance or mixture of substances intended to be used in the manufacture of a drug product, and that when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body. (TR74)

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)