NIIMBL Parameter Ontology
type: Ontology
label: Biopharma Parameter Ontology
abstract: This module contains terms and relations necessary for representing process intermediate and product quality attributes, process indicators and process parameters.
contributor: Adlane Rebai, Millipore Sigma
contributor: Ana Nikolov, OAGi
contributor: Boonserm Kulvatunyou, NIST
contributor: Cameron Gibbs, CrownPoint Technologies, LLC
contributor: Gabriela Henning, NIST
contributor: Jan Kemper, AstraZeneca
contributor: Marie-Aude Coutouly, Millipore Sigma
contributor: Melissa Weller, CrownPoint Technologies, LLC
contributor: Milos Drobnjakovic, OAGi
contributor: Stephen J. Granite, CrownPoint Technologies, LLC
contributor: Stephen Kahmann, CrownPoint Technologies, LLC
creator: NIIMBL BD-1 Ontology Group
license: http://opensource.org/licenses/MIT
imports: BiopharmaMaterial
imports: ReferenceOntologyCandidates
imports: TargetsLimitsRanges
imports: Core
version IRI: BiopharmaParameter
copyright: Copyright (c) 2022, 2023, 2024, 2025, 2026 Open Applications Group
maturity: Released

agitation rate
type: Class
subclass of: rate process profile
example: an agitation rate of 500 revolutions per minute applied by an impeller in a stirred gas-fermentation vessel; an agitation rate of 120 revolutions per minute applied by a stir bar during buffer preparation; an agitation rate of 30 rocking cycles per minute applied by a rocking bioreactor platform; an agitation rate of 180 shaking cycles per minute applied by an orbital shaker during flask cultivation;
adapted from: https://www.sciencedirect.com/topics/engineering/agitation-rate
explanatory note: Agitation rate is the rate of imposed mechanical motion used to stir, mix, shake, rock, or otherwise agitate a material. It should be distinguished from the resulting degree of mixing, gas transfer, bubble size distribution, mass transfer performance, or product yield, which may be affected by agitation rate but are not themselves agitation rates. Depending on the agitation mechanism, agitation rate may be expressed in revolutions per minute, cycles per minute, hertz, strokes per minute, or another unit appropriate to the motion.
first order logic axiom: AgitationRate(x) → RateProcessProfile(x)
is primitive: true
natural language definition: rate process profile at which imposed motion is applied to agitate a material
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is an 'agitation rate' then x is a 'rate process profile'

biological activity
type: Class
subclass of: Capability
subclass of: Restriction
  on property: capabilityOf
  some values from: Class
    union of: MaterialProduct
    union of: ProcessIntermediateMaterial
example: the target-binding biological activity of a monoclonal antibody drug product; the neutralizing biological activity of an antibody drug substance; the enzymatic biological activity of an enzyme therapeutic;
adapted from: https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf
explanatory note: Biological activity is modeled as the capability of a drug substance, drug product, or relevant process intermediate material to produce the biological effect for which it is being evaluated. It should be distinguished from drug potency: biological activity is the capability, while drug potency is the quality that characterizes the degree to which that biological activity is exhibited
first order logic axiom: BiologicalActivity(x) → Capability(x) ∧ ∃m ((MaterialProduct(m) ∨ ProcessIntermediateMaterial(m)) ∧ capabilityOf(x, m))
is primitive: true
natural language definition: capability of a drug substance, drug product, or relevant process intermediate material to achieve a defined biological effect
primitive rationale: There are insufficient constructs to create a set of necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'biological activity' then x is a 'capability' that is the 'capability of' some 'material product' or some 'process intermediate material'

biomass specific productivity
type: Class
subclass of: manufacturing process productivity
example: recombinant protein mass produced per hour per gram dry cell weight during microbial fermentation; enzyme activity units produced per hour per gram biomass during an E. coli expression process;
explanatory note: 1) In this context, biomass mass is commonly quantified as dry cell mass (e.g., dry cell weight), but may also be quantified using other biomass mass conventions (e.g., wet cell mass) when specified 2) Biomass mass may be the total biomass mass or, when specified, viable biomass mass.
first order logic axiom: BiomassSpecificProductivity(x) → ManufacturingProcessProductivity(x)
is primitive: true
natural language definition: manufacturing process productivity whose magnitude is normalized by biomass mass
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'biomass specific productivity' then x is a 'manufacturing process productivity'

biomolecule primary structure
type: Class
subclass of: BFO_0000019
subclass of: Restriction
  on property: BFO_0000164
  some values from: BiologicalSequence
subclass of: Restriction
  on property: qualityOf
  some values from: Class
    union of: DeoxyribonucleicAcid
    union of: Peptide
    union of: Protein
    union of: RibonucleicAcid
example: the primary structure of a monoclonal antibody heavy chain; the primary structure of a phosphorylated peptide; the primary structure of a methylated DNA molecule; the primary structure of an mRNA molecule; the primary structure of a protein variant with a single amino acid substitution
adapted from: http://www.bioassayontology.org/bao#BAO_0000013
explanatory note: Biomolecule primary structure may be described together with covalent modifications of particular residues, such as methylation or phosphorylation; these modifications do not change the linear residue order.
first order logic axiom: BiomoleculePrimaryStructure(x) → Quality(x) ∧ ∃m∃s((DeoxyribonucleicAcid(m) ∨ RibonucleicAcid(m) ∨ Peptide(m) ∨ Protein(m)) ∧ qualityOf(x,m) ∧ BiologicalSequence(s) ∧ concretizesAtAllTimes(x,s) ∧ genericallyDependsOnAtSomeTime(s,m))
is primitive: true
natural language definition: quality of a DNA, RNA, peptide, or protein molecule that is determined by the linear order of its nucleotide or amino acid residues
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'biomolecule primary structure' then x is a 'quality' that is the 'quality of' some 'deoxyribonucleic acid', 'ribonucleic acid', 'peptide', or 'protein' m and x 'concretizes at all times' some 'biological sequence' that 'generically depends on at some time' that same m

carbon dioxide evolution rate
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: processProfileOf
  some values from: Class
    intersection of: BFO_0000015
    intersection of: Restriction
      on property: BFO_0000057
      some values from: CellCulture
example: carbon dioxide evolution rate of a CHO fed-batch culture calculated from exhaust gas carbon dioxide concentration and gas flow rate;
first order logic axiom: CarbonDioxideEvolutionRate(x) → RateProcessProfile(x) ∧ ∃p(Process(p) ∧ processProfileOf(x,p) ∧ ∃c(CellCulture(c) ∧ hasParticipantAtSomeTime(p,c)))
is primitive: true
natural language definition: rate process profile at which carbon dioxide is produced by cells within a cell culture
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'carbon dioxide evolution rate' then x is a 'rate process profile' that is the 'process profile of' some 'process' that 'has participant at some time' some 'cell culture'

cell culture doubling time
type: Class
subclass of: BFO_0000202
example: the cell culture doubling time of a CHO cell population during seed train expansion; the cell culture doubling time calculated from viable cell density measurements during exponential growth; the cell culture doubling time of an E. coli culture during fermentation;
adapted from: http://purl.obolibrary.org/obo/MSIO_0000061
first order logic axiom: CellCultureDoublingTime(x) → TemporalInterval(x)
is primitive: true
natural language definition: temporal interval over which the size of a cell population doubles
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'cell culture doubling time' then x is a 'temporal interval'

cell population growth rate
type: Class
subclass of: population growth rate
subclass of: Restriction
  on property: BFO_0000057
  some values from: CellPopulation
example: cell population growth rate of a CHO cell population during fed-batch cultivation; viable cell population growth rate during seed train expansion;
first order logic axiom: CellPopulationGrowthRate(x) → PopulationGrowthRate(x) ∧ ∃c (CellPopulation(c) ∧ hasParticipantAtSomeTime(x, c))
is primitive: true
natural language definition: population growth rate of a cell population with respect to change in its number of cells
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'cell population growth rate' then x is a 'population growth rate' that 'has participant at some time' some 'cell population'

cell specific productivity
type: Class
subclass of: manufacturing process productivity
example: monoclonal antibody mass produced per viable cell per day during a CHO fed-batch culture; recombinant protein amount produced per cell per hour during a mammalian cell culture process;
first order logic axiom: CellSpecificProductivity(x) → ManufacturingProcessProductivity(x)
is primitive: true
natural language definition: manufacturing process productivity whose magnitude is normalized by cell amount, typically viable cell amount
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'cell specific productivity' then x is a 'manufacturing process productivity'

critical material attribute
type: Class
subclass of: input material attribute
equivalent class: Class
  intersection of: Class
    union of: BFO_0000019
    union of: Capability
  intersection of: Restriction
    on property: prescribedBy
    some values from: input critical material attribute specification
example: manganese concentration in a chemically defined medium whose variation can affect glycosylation of the output material; glucose concentration in a feed medium whose variation can affect glycan profile of the output material;
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: CriticalMaterialAttribute(x) ↔ (Quality(x) ∨ Capability(x)) ∧ ∃s(InputCriticalMaterialAttributeSpecification(s) ∧ prescribedBy(x, s))
natural language definition: quality or capability that is prescribed by an input critical material attribute specification
semi formal natural language definition: every instance of 'critical material attribute' is defined as exactly an instance of 'quality' or 'capability' that is 'prescribed by' some 'input critical material attribute specification'

critical process parameter
type: Class
subclass of: process parameter
equivalent class: Class
  intersection of: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
  intersection of: Restriction
    on property: prescribedBy
    some values from: critical process parameter specification
example: pH during the viral inactivation process; temperature during the fermentation process; agitation speed during the cell culture mixing step
abbreviation: CPP
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: CriticalProcessParameter(x) ↔ ∃s(CriticalProcessParameterSpecification(s) ∧ prescribedBy(x, s)) ∧ (TemporalRegion(x) ∨ ProcessProfile(x) ∨ Quality(x))
natural language definition: process profile or temporal region or quality prescribed by a critical process parameter specification
semi formal natural language definition: every instance of 'critical process parameter' is defined as exactly an instance that is either a 'temporal region' or a 'process profile' or 'quality' and that is 'prescribed by' some 'critical process parameter specification'

critical process parameter specification
type: Class
subclass of: process parameter specification
subclass of: Restriction
  on property: isAbout
  some values from: critical quality attribute specification
disjoint with: key process parameter specification
example: pH specification for the viral inactivation process, due to its impact on the viral clearance capability of the intermediate; temperature specification for the fermentation process, which affects product titer and impurity levels; agitation speed specification for the cell culture mixing step, where excessive shear stress can impact cell viability and product quality;
adapted from: https://database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf
explanatory note: FROM ICH: process parameter specification whose variability has an impact on a critical quality attribute and, therefore, should be monitored or controlled to ensure the process obtains the desired quality
first order logic axiom: CriticalProcessParameterSpecification(x) → ProcessParameterSpecification(x) ∧ ∃y (CriticalQualityAttributeSpecification(y) ∧ isAbout(x, y))
is primitive: true
natural language definition: process parameter specification that prescribes a variable which has an impact on a critical quality attribute
primitive rationale: There are insufficient constructs to have a set of necessary and sufficient conditions. In particular criticality determination is missing as well as a more semantically specific connection to a critical quality attribute specification
semi formal natural language axiom: if x is a 'critical process parameter specification' then x is a 'process parameter specification' and x 'is about' some 'critical quality attribute specification'

critical quality attribute
type: Class
subclass of: quality attribute
equivalent class: Class
  intersection of: Class
    union of: BFO_0000019
    union of: Capability
  intersection of: Restriction
    on property: prescribedBy
    some values from: critical quality attribute specification
example: host-cell protein impurity level in the clarified lysate; aggregate content in the purified monoclonal antibody; endotoxin level in the filled drug product; glycan composition of the monoclonal antibody drug substance
abbreviation: CQA
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: CriticalQualityAttribute(x) ↔ (Quality(x) ∨ Capability(x)) ∧ ∃s(CriticalQualityAttributeSpecification(s) ∧ prescribedBy(x, s))
natural language definition: quality or capability prescribed by a critical quality attribute specification
semi formal natural language definition: every instance of 'critical quality attribute' is defined as exactly an instance of 'quality' or 'capability' that is 'prescribed by' some 'critical quality attribute specification'

critical quality attribute specification
type: Class
subclass of: quality attribute specification
example: host-cell protein impurity specification in the clarified lysate; aggregate level specification for the purified monoclonal antibody; endotoxin level specification for the filled drug product; glycan profile specification for the monoclonal antibody drug substance
adapted from: https://database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf
explanatory note: 1) From ICH: critical quality attribute is a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. The deviations of CQAs beyond defined limits have significant adverse impacts on product quality and, therefore, mandate stringent control, monitoring, and validation measures. 2) This specification serves as a formal constraint on a quality attribute that is critical to product performance, safety, or efficacy, and is used to assess the acceptability of materials or products in manufacturing and quality control processes. 3) Critical quality attributes are monitored throughout the manufacturing process and as such are measured on attributes of both final products and intermediate materials generated during the product production process.
first order logic axiom: CriticalQualityAttributeSpecification(x) → QualityAttributeSpecification(x)
is primitive: true
natural language definition: quality attribute specification that prescribes some quality, capability, constitution, or composition deemed critical to ensuring the safety, efficacy, or performance of a material product
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions. In particular criticality determination is missing
semi formal natural language axiom: if x is a 'critical quality attribute specification' then x is a 'quality attribute specification'

culture split ratio
type: Class
subclass of: Ratio
example: 1:3 culture split ratio in which one flask of cell culture is divided to establish three resulting flasks; 1:5 culture split ratio in which one part of source cell culture is transferred according to a passaging protocol and fresh medium is added to establish the resulting culture; 1:10 culture split ratio used during suspension-cell passaging to reduce culture density for continued growth; 1:2 culture split ratio in which a recovered culture is divided to establish two resulting cultures
adapted from: https://www.atcc.org/resources/culture-guides/animal-cell-culture-guide
first order logic axiom: CultureSplitRatio(x) → Ratio(x)
is primitive: true
natural language definition: ratio of a source cell culture to one or more resulting cell cultures established from that source culture during passaging
primitive rationale: There are insufficient constructs to create a set of necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'culture split ratio' then x is a 'ratio'
synonym: subculturing ratio

dissolution rate
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: BFO_0000057
  some values from: Solute
subclass of: Restriction
  on property: processProfileOf
  some values from: Class
    intersection of: BFO_0000015
    intersection of: Restriction
      on property: BFO_0000057
      some values from: Solvent
example: dissolution rate of sodium chloride in water during buffer preparation; dissolution rate of powdered cell culture medium in water during media preparation; dissolution rate of sucrose in an aqueous reaction mixture; dissolution rate of an active pharmaceutical ingredient during formulation development;
adapted from: https://www.fda.gov/media/148472/download and https://www.ncbi.nlm.nih.gov/books/NBK431100/#:~:text=%5B1%5D%5B2%5D%5B,/L%20or%20g/L
explanatory note: Dissolution rate describes how fast a solute enters solution under defined conditions and is typically expressed as an amount (or concentration) dissolved per unit time. It is a non-equilibrium, time-dependent behavior that precedes attainment of the solubility limit (equilibrium saturation). Dissolution occurs at the solid–liquid interface, where solvent contacts the solid surface and solute molecules detach and diffuse into the bulk liquid. The observed rate is governed by the solute’s surface area and physical form (e.g., particle size and wetting), solute–solvent interactions, temperature, mixing/agitation (hydrodynamics), and mass-transfer factors such as diffusion boundary layer thickness, as well as the driving force to saturation (difference between the saturation concentration and the current bulk concentration). Experimentally, dissolution rate is determined by monitoring how dissolved concentration (or dissolved mass) changes over time under a specified method, and it is used to evaluate and control how quickly solid components (e.g., salts, buffers, active ingredients) reach the required dissolved state in process preparation and formulation contexts.
first order logic axiom: DissolutionRate(x) → RateProcessProfile(x) ∧ ∃s (Solute(s) ∧ hasParticipantAtSomeTime(x, s)) ∧ ∃p (Process(p) ∧ processProfileOf(x, p) ∧ ∃v (Solvent(v) ∧ hasParticipantAtSomeTime(p, v)))
is primitive: true
natural language definition: rate process profile at which a solute dissolves in a solvent
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'dissolution rate' then x is a 'rate process profile' that 'has participant at some time' some 'solute' and is the 'process profile of' some 'process' that 'has participant at some time' some 'solvent'

drug potency
type: Class
subclass of: BFO_0000019
subclass of: Restriction
  on property: BFO_0000195
  some values from: biological activity
subclass of: Restriction
  on property: qualityOf
  some values from: Class
    union of: MaterialProduct
    union of: ProcessIntermediateMaterial
example: the drug potency of a monoclonal antibody drug product determined by a cell-based neutralization assay; the drug potency of an enzyme therapeutic drug substance determined by an enzymatic activity assay; the drug potency of a cytokine drug product determined by a receptor-mediated bioassay; the drug potency of a vaccine antigen lot determined by an immunological potency assay
adapted from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-production-characterisation-and-specification-monoclonal-antibodies-and-related-products-revision-1_en.pdf and https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-6-b-test-procedures-and-acceptance-criteria-biotechnologicalbiological-products-step-5_en.pdf
explanatory note: According to ICH Q6B, a relevant validated potency assay should ordinarily be part of the specification for a biotechnological or biological drug substance or drug product. In justified cases, physicochemical methods may be used for quantitative assessment when sufficient physicochemical information is available, an appropriate correlation with biological activity has been demonstrated, and the manufacturing history or corresponding cross-stage assay strategy supports their use. Potency should be distinguished from a simple determination of product quantity because it characterizes the degree of the relevant biological activity.
first order logic axiom: DrugPotency(x) → Quality(x) ∧ ∃m∃a((MaterialProduct(m) ∨ ProcessIntermediateMaterial(m)) ∧ qualityOf(x,m) ∧ BiologicalActivity(a) ∧ capabilityOf(a,m) ∧ specificallyDependsOn(x,a))
is primitive: true
natural language definition: quality of a drug substance, drug product, or relevant process intermediate material that is the quantitative degree of its biological activity
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'drug potency' then x is a 'quality' that is the 'quality of' some 'material product' or 'process intermediate material' m and 'specifically depends on' some 'biological activity' that is the 'capability of' that same m

flow rate
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: BFO_0000057
  some values from: BFO_0000040
example: mass flow rate of air supplied to a bioreactor sparger; mass flow rate of carbon dioxide in an exhaust gas stream; volumetric flow rate of buffer through a chromatography column; volumetric flow rate of permeate through an ultrafiltration membrane
adapted from: http://purl.obolibrary.org/obo/PATO_0001574
first order logic axiom: FlowRate(x) → RateProcessProfile(x) ∧ ∃m(MaterialEntity(m) ∧ hasParticipantAtSomeTime(x,m))
is primitive: true
natural language definition: rate process profile at which material is transported across a specified surface or boundary
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'flow rate' then x is a 'rate process profile' that 'has participant at some time' some 'material entity'

input critical material attribute specification
type: Class
subclass of: input material attribute specification
example: the CMA specification for manganese concentration in a chemically defined medium when variation in manganese concentration can affect glycosylation of the output material; the CMA specification for glucose concentration in a feed medium when variation in glucose concentration can affect glycan profile of the output material; the CMA specification for culture medium osmolality when variation in osmolality can affect charge variant profile or aggregation level of the output material;
abbreviation: CMA specification
adapted from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4070262/
first order logic axiom: InputCriticalMaterialAttributeSpecification(x) → InputMaterialAttributeSpecification(x)
is primitive: true
natural language definition: input material attribute specification that prescribes some quality, capability, constitution, or composition whose variation can have a significant impact on the quality of the output material
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is an 'input critical material attribute specification' then x is an 'input material attribute specification'

input material attribute
type: Class
subclass of: BFO_0000020
equivalent class: Class
  intersection of: Class
    union of: BFO_0000019
    union of: Capability
  intersection of: Restriction
    on property: prescribedBy
    some values from: input material attribute specification
example: pH of a buffer used for elution; vitamin concentration of a cell culture medium used in a production culture process;
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: InputMaterialAttribute(x) ↔ (Quality(x) ∨ Capability(x)) ∧ ∃s(InputMaterialAttributeSpecification(s) ∧ prescribedBy(x, s))
natural language definition: quality or capability that is prescribed by an input material attribute specification
semi formal natural language definition: every instance of 'input material attribute' is defined as exactly an instance of 'quality' or 'capability' that is 'prescribed by' some 'input material attribute specification'

input material attribute specification
type: Class
subclass of: InputSpecification
subclass of: Class
  union of: Restriction
    on property: prescribes
    some values from: Class
      intersection of: Class
        union of: BFO_0000019
        union of: Capability
      intersection of: Restriction
        on property: BFO_0000197
        some values from: Class
  union of: Restriction
    on property: prescribes
    some values from: Class
      intersection of: Class
        union of: BFO_0000019
        union of: Capability
      intersection of: Restriction
        on property: BFO_0000197
        some values from: Class
example: the input material attribute specification for pH of a buffer used as an input material; the input material attribute specification for osmolality of a culture medium used as an input material; the input material attribute specification for glucose concentration in a feed medium;
adapted from: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf and https://pmc.ncbi.nlm.nih.gov/articles/PMC4070262/
explanatory note: Input materials can be raw materials, process intermediate materials, or production consumables, which is reflected in the prescription axiom
first order logic axiom: InputMaterialAttributeSpecification(x) → InputSpecification(x) ∧ ∃a (prescribes(x, a) ∧ (Quality(a) ∨ Capability(a)) ∧ ∃m (inheresIn(a, m) ∧ ((RawMaterial(m) ∨ ProcessIntermediateMaterial(m) ∨ ProductionConsumable(m)) ∨ (MaterialEntity(m) ∧ ∃w (continuantPartOfAtAllTimes(m, w) ∧ (RawMaterial(w) ∨ ProcessIntermediateMaterial(w) ∨ ProductionConsumable(w)))))))
is primitive: true
natural language definition: input specification that prescribes some quality, capability, constitution, or composition of an input material that can have an impact on process performance or on the quality of the output material
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is an 'input material attribute specification' then x is an 'input specification' that 'prescribes' some 'quality' or 'capability' that 'inheres in' either some 'raw material', 'process intermediate material', or 'production consumable', or in some 'material entity' that is a 'continuant part of at all times' some 'raw material', 'process intermediate material', or 'production consumable'

key performance indicator
type: Class
subclass of: performance indicator
equivalent class: Class
  intersection of: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
    union of: ProcessCharacteristic
  intersection of: Restriction
    on property: prescribedBy
    some values from: key performance indicator specification
example: average deviation rate per production step due to CPP excursions; yield consistency over successive purification runs; final harvest titer for a specific production batch; Viral clearance log reduction amount for the purification step; batch release time within the specified regulatory window
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: KeyPerformanceIndicator(x) ↔ ∃s (KeyPerformanceIndicatorSpecification(s) ∧ prescribedBy(x, s)) ∧ (TemporalRegion(x) ∨ ProcessProfile(x) ∨ Quality(x) ∨ ProcessCharacteristic(x))
natural language definition: process profile, temporal region, quality or process characteristic prescribed by a key performance indicator specification
semi formal natural language definition: every instance of 'key performance indicator' is defined as exactly an instance that is either a 'temporal region', 'process profile', 'quality', or 'process characteristic' and that is 'prescribed by' some 'key performance indicator specification'

key performance indicator specification
type: Class
subclass of: performance indicator specification
example: final harvest titer specification for the production batch, measured in pooled harvested cell culture fluid at completion of harvest, with a target range of 3.5 to 5.0 grams per liter; viral clearance log reduction value specification for the purification step, calculated from the viral loads measured before and after the step, with a target of at least 4.0; batch release cycle time specification for the production batch, measured from completion of manufacturing to authorization of the batch for release, with a target of no more than 10 calendar days
adapted from: ISO-22400 and https://www.gmp-compliance.org/gmp-news/fdas-current-thinking-on-kpis-and-quality-metrics
explanatory note: 1) Per the ISO-22400 standard a good KPI has certain criteria which ensure its usefulness in achieving various goals in the manufacturing operation. For more details the user should take a look at the standard. Also the KPI specification should contain information about its context, including timing, audience, production methodology, effect model diagram, and notes. 2) In (bio)pharmaceutical manufacturing, some process-focused KPIs may be related to CQAs and influenced by CPPs. Such KPIs can provide evidence of process consistency, reproducibility, or performance and can support assessment of whether manufacturing steps are proceeding as expected. Other KPIs may address operational performance, such as throughput, cycle time, equipment utilization, or schedule adherence, without being directly related to CQAs or CPPs.
first order logic axiom: KeyPerformanceIndicatorSpecification(x) → PerformanceIndicatorSpecification(x)
is primitive: true
natural language definition: performance indicator specification that prescribes a measurable characteristic whose measurements reflect effectiveness with respect to some objective determined as important by a person or organization
primitive rationale: This term is expected to remain primitive as different organizations have different criteria for establishing what is key.
semi formal natural language axiom: if x is a 'key performance indicator specification' then x is a 'performance indicator specification'

key process parameter
type: Class
subclass of: process parameter
equivalent class: Class
  intersection of: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
  intersection of: Restriction
    on property: prescribedBy
    some values from: key process parameter specification
example: temperature during media hold; buffer addition flow rate during diafiltration
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: KeyProcessParameter(x) ↔ ∃s(KeyProcessParameterSpecification(s) ∧ prescribedBy(x, s)) ∧ (TemporalRegion(x) ∨ ProcessProfile(x) ∨ Quality(x))
natural language definition: process profile, temporal region, or quality prescribed by a key process parameter specification
semi formal natural language definition: every instance of 'key process parameter' is defined as exactly an instance that is either a 'temporal region' or a 'process profile' or 'quality' and that is 'prescribed by' some 'key process parameter specification'

key process parameter specification
type: Class
subclass of: process parameter specification
example: temperature specification for media hold, which is necessary to prevent microbial growth without affecting downstream CQAs; flow rate specification for diafiltration buffer addition, important for maintaining steady-state conditions but not directly impacting product purity;
adapted from: https://www.biophorum.com/wp-content/uploads/bp_downloads/CPV-Case-Study-Interactive-Version.pdf
first order logic axiom: KeyProcessParameterSpecification(x) → ProcessParameterSpecification(x)
is primitive: true
natural language definition: process parameter specification that prescribes a variable which must be tightly controlled to ensure process consistency and that does not directly impact any critical quality attribute
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'key process parameter specification' then x is a 'process parameter specification'

manufacturing process productivity
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: BFO_0000057
  some values from: Class
    union of: MaterialProduct
    union of: ProcessIntermediateMaterial
subclass of: Restriction
  on property: processProfileOf
  some values from: Class
    intersection of: ManufacturingProcess
    intersection of: Restriction
      on property: hasSpecifiedOutput
      some values from: Class
        union of: MaterialProduct
        union of: ProcessIntermediateMaterial
example: monoclonal antibody mass produced per day during a fed-batch manufacturing process; recombinant enzyme activity units produced per hour during a microbial fermentation process;
explanatory note: Manufacturing process productivity concerns production of process intermediate material or material product per unit time. It should be distinguished from labor productivity, equipment effectiveness, process yield, resource efficiency, and economic productivity.
first order logic axiom: ManufacturingProcessProductivity(x) → RateProcessProfile(x) ∧ ∃m∃p((ProcessIntermediateMaterial(m) ∨ MaterialProduct(m)) ∧ ManufacturingProcess(p) ∧ hasParticipantAtSomeTime(x,m) ∧ processProfileOf(x,p) ∧ hasSpecifiedOutput(p,m))
is primitive: true
natural language definition: rate process profile at which process intermediate material or material product is produced in a manufacturing process under specified conditions
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'manufacturing process productivity' then x is a 'rate process profile' that 'has participant at some time' some 'process intermediate material' or 'material product' m and is the 'process profile of' some 'manufacturing process' that 'has specified output' that same m

mass flow rate
type: Class
subclass of: flow rate
example: mass flow rate of air supplied to a bioreactor sparger; mass flow rate of carbon dioxide in an exhaust gas stream; mass flow rate of buffer through a chromatography column; mass flow rate of liquid feed through a process line
adapted from: https://www.alicat.com/support/what-is-the-difference-between-mass-flow-and-volumetric-flow/
first order logic axiom: MassFlowRate(x) → FlowRate(x)
is primitive: true
natural language definition: flow rate whose magnitude is determined by the mass of material transported across the specified surface or boundary per unit of elapsed time
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'mass flow rate' then x is a 'flow rate'

metabolite uptake rate
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: BFO_0000057
  some values from: MolecularEntity
subclass of: Restriction
  on property: processProfileOf
  some values from: Class
    intersection of: BFO_0000015
    intersection of: Restriction
      on property: BFO_0000057
      some values from: CellCulture
example: glucose uptake rate by a CHO cell population during fed-batch cultivation; glutamine uptake rate by a mammalian cell culture during early growth phase; amino acid uptake rate by a cell population during a nutrient-limited culture process;
first order logic axiom: MetaboliteUptakeRate(x) → RateProcessProfile(x) ∧ ∃p(Process(p) ∧ processProfileOf(x,p) ∧ ∃c(CellCulture(c) ∧ hasParticipantAtSomeTime(p,c))) ∧ ∃me(MolecularEntity(me) ∧ hasParticipantAtSomeTime(x,me))
is primitive: true
natural language definition: rate process profile at which a metabolite is taken up by cells within a cell culture
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'metabolite uptake rate' then x is a 'rate process profile' that is the 'process profile of' some 'process' that 'has participant at some time' some 'cell culture' and x 'has participant at some time' some 'molecular entity'

normalized flow rate
type: Class
subclass of: flow rate
example: permeate flow rate normalized to membrane area during ultrafiltration, expressed as L m⁻² h⁻¹; a perfusion culture operated at 1 VVD, meaning one working volume of medium is exchanged over one day;
explanatory note: The reference quantity used for normalization may be, for example, membrane area, working volume, or cell amount. The resulting normalized flow rate may therefore have different units depending on the reference quantity. Normalization in this sense does not refer to conversion of a gas flow rate to standard or normal temperature and pressure conditions.
first order logic axiom: NormalizedFlowRate(x) → FlowRate(x)
is primitive: true
natural language definition: flow rate whose magnitude is expressed relative to a specified reference quantity
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'normalized flow rate' then x is a 'flow rate'

oxygen uptake rate
type: Class
subclass of: rate process profile
subclass of: Restriction
  on property: BFO_0000057
  some values from: DioxygenMolecule
subclass of: Restriction
  on property: processProfileOf
  some values from: Class
    intersection of: BFO_0000015
    intersection of: Restriction
      on property: BFO_0000057
      some values from: CellCulture
example: oxygen uptake rate of a CHO cell culture during fed-batch cultivation; oxygen uptake rate of an E. coli fermentation during exponential growth;
first order logic axiom: OxygenUptakeRate(x) → RateProcessProfile(x) ∧ ∃o (DioxygenMolecule(o) ∧ hasParticipantAtSomeTime(x, o)) ∧ ∃p (Process(p) ∧ processProfileOf(x, p) ∧ ∃c (CellCulture(c) ∧ hasParticipantAtSomeTime(p, c)))
is primitive: true
natural language definition: rate process profile at which oxygen is consumed by cells within a cell culture
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is an 'oxygen uptake rate' then x is a 'rate process profile' that 'has participant at some time' some 'dioxygen molecule' and is the 'process profile of' some 'process' that 'has participant at some time' some 'cell culture'

performance indicator
type: Class
subclass of: BFO_0000001
equivalent class: Class
  intersection of: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
    union of: ProcessCharacteristic
  intersection of: Restriction
    on property: prescribedBy
    some values from: performance indicator specification
example: Yearly sales, monthly throughput, quarterly overall equipment effectiveness, 12-month on-time delivery percentage.
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: PerformanceIndicator(x) ↔ ∃s (PerformanceIndicatorSpecification(s) ∧ prescribedBy(x, s)) ∧ (TemporalRegion(x) ∨ ProcessProfile(x) ∨ Quality(x) ∨ ProcessCharacteristic(x))
natural language definition: process profile, temporal region, quality or process characteristic prescribed by a performance indicator specification
semi formal natural language definition: every instance of 'performance indicator' is defined as exactly an instance that is either a 'temporal region', 'process profile', 'quality', or 'process characteristic' and that is 'prescribed by' some 'performance indicator specification'

performance indicator specification
type: Class
subclass of: InformationContentEntity
subclass of: Restriction
  on property: isAbout
  some values from: ObjectiveSpecification
subclass of: Restriction
  on property: prescribes
  some values from: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
    union of: ProcessCharacteristic
example: annual sales revenue specification for the organization for the applicable fiscal year, with a target of at least USD 10 million; monthly production throughput specification for the manufacturing line, expressed as conforming units completed per operating hour, with a target range of 120 to 150 units per hour; quarterly overall equipment effectiveness specification for the production line, calculated as availability multiplied by performance multiplied by quality, with a target of at least 85 percent; rolling 12-month on-time delivery percentage specification for customer orders, calculated from orders delivered on or before the committed delivery date relative to the applicable orders in the reporting period, with a target of at least 95 percent
adapted from: https://database.ich.org/sites/default/files/Q10%20Guideline.pdf and ISO 22400
explanatory note: 1) Performance indicators are: Measurable: It’s based on quantifiable data (e.g. percentages, counts, ratios). Goal-oriented: It reflects progress toward a defined objective. Actionable: It provides insight into what’s working and what might need improvement. 2) Also they are typically: S: Specific M: Measurable A: Achievable R: Relevant T: Time bound 3) A performance indicator differs from a process parameter in that it is typically not directly controllable. Instead, it often reflects the combined effect of multiple process parameters. For example, production yield is a performance indicator that may be influenced by parameters such as temperature, pH, and agitation speed.
first order logic axiom: PerformanceIndicatorSpecification(x) → InformationContentEntity(x) ∧ ∃y ( (TemporalRegion(y) ∨ Quality(y) ∨ ProcessProfile(y) ∨ProcessCharacteristic(y)) ∧ prescribes(x, y) ) ∧ ∃z ( ObjectiveSpecification(z) ∧ isAbout(x, z))
is primitive: true
natural language definition: information content entity that prescribes some measurable characteristic whose measurements reflect the effectiveness of an agent, planned process, organization, or piece of equipment with respect to a particular objective
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions. As an example there is currently no construct to reflect if a characteristic is measurable
semi formal natural language axiom: if x is a 'performance indicator specification' then x is an 'information content entity' and x 'prescribes' some 'temporal region' or 'quality' or 'process profile' or 'process characteristic' and x 'is about' some 'objective specification'
usage note: Measurable characteristics in this case can be some quality, temporal region, process profile or process characteristic which is reflected in the axiom.

planned process yield
type: Class
subclass of: ProcessCharacteristic
subclass of: Restriction
  on property: processCharacteristicOf
  some values from: Class
    intersection of: PlannedProcess
    intersection of: Restriction
      on property: hasSpecifiedOutput
      some values from: BFO_0000040
example: the yield of a purification step calculated as purified protein mass relative to protein mass loaded onto the column; the yield of a synthesis process calculated as actual product amount relative to theoretical product amount; the yield of a harvest process calculated as recovered product amount relative to product amount present before harvest;
explanatory note: The specified reference quantity is a quantity associated with a participant in the planned process, such as an input quantity, starting-material quantity, limiting-component quantity, theoretical output quantity, expected output quantity, or intermediate-material quantity. Planned process yield should be distinguished from the output quantity itself: 8 g of purified protein is an output quantity, whereas 80% yield is a process characteristic relating the output quantity to a specified reference quantity.
first order logic axiom: PlannedProcessYield(x) → ProcessCharacteristic(x) ∧ ∃p (PlannedProcess(p) ∧ processCharacteristicOf(x, p) ∧ ∃o (MaterialEntity(o) ∧ hasSpecifiedOutput(p, o)))
is primitive: true
natural language definition: process characteristic that is the ratio of a specified output quantity produced in a planned process to a specified reference quantity associated with that planned process
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'planned process yield' then x is a 'process characteristic' that is the 'process characteristic of' some 'planned process' that 'has specified output' some 'material entity'

population growth rate
type: Class
subclass of: rate process profile
example: population growth rate of a CHO cell population during fed-batch cultivation; population growth rate of an E. coli population during exponential growth; viable cell population growth rate during seed train expansion; microbial population growth rate during fermentation
first order logic axiom: PopulationGrowthRate(x) → RateProcessProfile(x)
is primitive: true
natural language definition: rate process profile that captures change in the size of a population per unit of elapsed time
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'population growth rate' then x is a 'rate process profile'

process parameter
type: Class
subclass of: BFO_0000001
equivalent class: Class
  intersection of: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
  intersection of: Restriction
    on property: prescribedBy
    some values from: process parameter specification
example: agitation speed during the mixing process in a cell culture step; incubation time of the cell expansion process; temperature during the fermentation process; flow rate during the loading phase of a chromatography process; pH of the solution in the neutralization process; residence time in the viral inactivation process
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: ProcessParameter(x) ↔ ∃s(ProcessParameterSpecification(s) ∧ prescribedBy(x, s)) ∧ (TemporalRegion(x) ∨ ProcessProfile(x) ∨ Quality(x))
natural language definition: process profile or temporal region or quality prescribed by a process parameter specification
semi formal natural language definition: every instance of 'process parameter' is defined as exactly an instance that is either a 'temporal region' or a 'process profile' or 'quality' and that is 'prescribed by' some 'process parameter specification'

process parameter specification
type: Class
subclass of: InformationContentEntity
subclass of: Restriction
  on property: BFO_0000177
  some values from: PlanSpecification
subclass of: Restriction
  on property: prescribes
  some values from: Class
    union of: BFO_0000008
    union of: BFO_0000019
    union of: BFO_0000144
disjoint with: quality attribute specification
example: agitation speed specification for the mixing process in a cell culture step; incubation time specification for the cell expansion process; temperature specification for the fermentation process; flow rate specification for the loading phase of a chromatography process; pH specification for the neutralization process in buffer preparation; residence time specification for the viral inactivation process
adapted from: https://www.biophorum.com/wp-content/uploads/bp_downloads/CPV-Case-Study-Interactive-Version.pdf; https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-manufacture-finished-dosage-form-revision-1_en.pdf and ISA88
counter example: a material specification for a raw material, which defines material properties rather than process behavior; and a specification stating the amount of glucose to be added to a bioreactor, which is an input specification describing material inputs rather than a process parameter; model number of a chromatography column or chromatography type (affinity)
explanatory note: 1) Process parameters must be specified with their target value or acceptable range. A process parameter may be critical or non-critical. 2) Ranges for process parameters are established during process development, and changes to operating ranges will be managed within the quality system. 3) Process parameters are used to describe and control the conditions under which a process operates, ensuring that the process achieves its intended results. 4) Process parameters are essential for defining how a process should be carried out and are typically specified in process documentation or recipes. They provide the necessary details for operators and control systems to maintain the process within desired conditions, supporting consistent product quality and process performance.
first order logic axiom: ProcessParameterSpecification(x) → InformationContentEntity(x) ∧ ∃y (PlanSpecification(y) ∧ continuantPartOfAtAllTimes(x, y)) ∧ ∃z ((TemporalRegion(z) ∨ ProcessProfile(z) ∨ Quality(z)) ∧ prescribes(x, z))
is primitive: true
natural language definition: information content entity that prescribes a monitorable or controllable variable associated with some planned process
primitive rationale: There are insufficient constructs to represent monitorable and controllable.
semi formal natural language axiom: if x is a 'process parameter specification' then x is an 'information content entity' and x is a 'continuant part of at all times' some 'plan specification' and x 'prescribes' some 'temporal region' or 'process profile' or 'quality'
usage note: Process parameter specifications are used to prescribe process parameters, which may take the form of process profiles, qualities, or temporal regions. Process profiles may reflect the realization of capabilities inhering in equipment or consumables, such as the agitation speed of an impeller, or describe dynamic properties of participating entities, such as the flow rate of a fluid stream or the sampling frequency in a monitoring subprocess. Temporal parameters, such as incubation time or residence time, are modeled as temporal regions that represent the duration or timing of a process or subprocess. Qualities refer to intrinsic characteristics of process participants, such as temperature, pH, pressure, or concentration, which are constrained or controlled during the process. When prescribed by a specification, these qualities represent targeted or acceptable ranges of measurable features during the process. The axiom that a process parameter specification must prescribe some temporal region, process profile, or quality formally captures the scope of what qualifies as a process parameter.

product titer
type: Class
subclass of: Concentration
subclass of: Restriction
  on property: qualityOf
  some values from: Class
    union of: MaterialProduct
    union of: ProcessIntermediateMaterial
example: titer of 3.2 g/L monoclonal antibody in a cell culture harvest on day 14; titer of 2.8 g/L monoclonal antibody in a clarified harvest after depth filtration; titer of 12 g/L monoclonal antibody in a protein A eluate after elution;
explanatory note: 1) In this context, ‘target product’ denotes the specified substance of interest for the manufacturing objective and may be a drug substance, process intermediate, or other designated active or functional component. Product titer is evaluated at a specified time point and may vary over time due to dilution, degradation, or changes in process volume. 2) Here, process material means a material that is being transformed or modified in a manufacturing process, including process intermediate material and the material product. It does not include raw materials or consumables.
first order logic axiom: ProductTiter(x) → Concentration(x) ∧ ∃m ((ProcessIntermediateMaterial(m) ∨ MaterialProduct(m)) ∧ qualityOf(x, m))
is primitive: true
natural language definition: concentration of a process intermediate material or material product that is determined by the amount of a target product in that process intermediate material or material product per unit volume
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'product titer' then x is a 'concentration' that is the 'quality of' some 'process intermediate material' or some 'material product'

protein secondary structure
type: Class
subclass of: PhysicalStructure
subclass of: Restriction
  on property: qualityOf
  some values from: Protein
example: the alpha-helical secondary structure of a protein; the beta-sheet secondary structure of an antibody domain; the turn structure connecting two beta strands in a protein; the loop structure in an enzyme active-site region; the altered secondary structure of a protein after thermal stress
adapted from: https://www.fda.gov/media/182387/download
first order logic axiom: ProteinSecondaryStructure(x) → PhysicalStructure(x) ∧ ∃p (Protein(p) ∧ qualityOf(x, p))
is primitive: true
natural language definition: physical structure of a protein that is the local three-dimensional arrangement of segments of its polypeptide backbone, commonly characterized by recurring backbone hydrogen-bonding patterns
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'protein secondary structure' then x is a 'physical structure' that is the 'quality of' some 'protein'

protein tertiary structure
type: Class
subclass of: PhysicalStructure
subclass of: Restriction
  on property: qualityOf
  some values from: Protein
example: the folded three-dimensional structure of a single-domain antibody molecule; the folded structure of an antibody-derived single-chain variable fragment; the folded structure of a recombinant human growth hormone molecule; the folded three-dimensional structure of an erythropoietin molecule stabilized by disulfide bonds and glycosylation; the compact globular structure of a myoglobin molecule; the beta-barrel structure of a green fluorescent protein molecule
adapted from: https://www.fda.gov/media/182387/download
first order logic axiom: ProteinTertiaryStructure(x) → PhysicalStructure(x) ∧ ∃p (Protein(p) ∧ qualityOf(x, p))
is primitive: true
natural language definition: physical structure of a protein that is the overall three-dimensional arrangement arising from the conformation of its polypeptide chain, including the spatial organization of its secondary structure elements relative to one another
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'protein tertiary structure' then x is a 'physical structure' that is the 'quality of' some 'protein'

quality attribute
type: Class
subclass of: BFO_0000020
equivalent class: Class
  intersection of: Class
    union of: BFO_0000019
    union of: Capability
  intersection of: Restriction
    on property: prescribedBy
    some values from: quality attribute specification
example: content uniformity of the dosage units in a batch; level of degradation products in the formulation; residual solvent level in the final product; dissolution capability of a dosage form; moisture content of the drug product; microbial load in the final product; color of the tablet or capsule; shape of the dosage form; size of the finished unit; odor of the drug product;
counter example: yield of the protein purification step
explanatory note: See the expanded definition under the corresponding specification class. The term is formalized here as a defined class by referring to its corresponding specification class and exists primarily for ontological modeling and implementation convenience.
first order logic definition: QualityAttribute(x) ↔ (Quality(x) ∨ Capability(x)) ∧ ∃s(QualityAttributeSpecification(s) ∧ prescribedBy(x, s))
natural language definition: quality or capability that is prescribed by a quality attribute specification
semi formal natural language definition: every instance of 'quality attribute' is defined as exactly an instance of 'quality' or 'capability' that is 'prescribed by' some 'quality attribute specification'

quality attribute specification
type: Class
subclass of: OutputObjectiveSpecification
subclass of: Class
  union of: Restriction
    on property: prescribes
    some values from: Class
      intersection of: Class
        union of: BFO_0000019
        union of: Capability
      intersection of: Restriction
        on property: BFO_0000197
        some values from: Class
  union of: Restriction
    on property: prescribes
    some values from: Class
      intersection of: Class
        union of: BFO_0000019
        union of: Capability
      intersection of: Restriction
        on property: BFO_0000197
        some values from: Class
example: content uniformity specification; degradation product specification; residual solvent specification; drug release specification; dissolution specification; moisture content specification; microbial limit specification; color specification; shape specification; size specification; odor specification;
adapted from: https://www.biophorum.com/wp-content/uploads/bp_downloads/CPV-Case-Study-Interactive-Version.pdf and https://pmc.ncbi.nlm.nih.gov/articles/PMC4070262/pdf/12248_2014_Article_9598.pdf
counter example: Specification stating that purification yield must be ≥ 70% - This is a process performance constraint, not a specification for a quality of the product or process intermediate material.
explanatory note: Attributes can be critical or not critical. In pharma criticality of an attribute is primarily based upon the severity of harm to the patient should the product fall outside the acceptable range for that attribute. Probability of occurrence, detectability, or controllability does not impact criticality of an attribute.
first order logic axiom: QualityAttributeSpecification(x) → OutputObjectiveSpecification(x) ∧ ∃q∃m((Quality(q) ∨ Capability(q)) ∧ (ProcessIntermediateMaterial(m) ∨ MaterialProduct(m)) ∧ ((∃z(MaterialEntity(z) ∧ continuantPartOfAtAllTimes(z, m) ∧ inheresIn(q, z))) ∨ inheresIn(q, m)) ∧ prescribes(x, q))
is primitive: true
natural language definition: output objective specification that prescribes some quality, capability, constitution, or composition that a material product or process intermediate material must possess in order to satisfy predefined quality requirements
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions. Specifically the constructs for predefined quality requirements are missing.
semi formal natural language axiom: if x is a 'quality attribute specification' then x is an 'output objective specification' that 'prescribes' some 'quality' or 'capability' q that either 'inheres in' some 'process intermediate material' or 'material product' m, or 'inheres in' some 'material entity' z that is a 'continuant part of at all times' m
usage note: These specifications may refer to intrinsic physical or chemical properties (such as pH or viscosity), to capabilities (such as binding affinity), or to the identity and proportion of distinguishable components (such as glycoforms, excipients, or host cell proteins). In cases where constitution or composition is relevant, the specification typically should be modeled as a quality that inheres in a continuant part of the material, such as the concentration or proportion of a specific component which is the 'quality of' (inheres in) that specific component.

rate process profile
type: Class
subclass of: BFO_0000144
example: glucose consumption rate during a fed-batch cell culture process; product formation rate during a fermentation process; biomass formation rate during microbial cultivation; feed addition rate during a material feeding process; number of Tetra Pak cartons filled per hour by a packaging line; rate of potable water output from a water treatment plant
adapted from: http://purl.allotrope.org/ontologies/process#AFP_0003454 and http://purl.allotrope.org/ontologies/result#AFR_0000954 and https://philpapers.org/archive/SMICPA-5.pdf
explanatory note: An attribute captured by a rate process profile may itself be represented by another process profile, as when an acceleration profile captures variation in a speed profile per unit of elapsed time.
first order logic axiom: RateProcessProfile(x) → ProcessProfile(x)
is primitive: true
natural language definition: process profile that captures variation in an attribute of a process or one of its participants per unit of elapsed time
primitive rationale: This term is expected to be further formalized in the IOF Core.
semi formal natural language axiom: if x is a 'rate process profile' then x is a 'process profile'

specific cell population growth rate
type: Class
subclass of: cell population growth rate
example: specific growth rate of an E. coli population during exponential growth; specific cell population growth rate of a CHO cell population during seed train expansion; specific growth rate calculated from viable cell density measurements over a defined interval;
first order logic axiom: SpecificCellPopulationGrowthRate(x) → CellPopulationGrowthRate(x)
is primitive: true
natural language definition: cell population growth rate whose magnitude is normalized by the size of that cell population
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'specific cell population growth rate' then x is a 'cell population growth rate'

total material added
type: Class
subclass of: ProcessCharacteristic
subclass of: Restriction
  on property: processCharacteristicOf
  some values from: PlannedProcess
example: a viral inactivation process has total material added of 0.5 L acid solution from a single bolus addition for pH adjustment; a production culture process has total material added of 73 g galactose from multiple bolus additions during the production phase; a chromatography column equilibration process has total material added of 6 column volumes of equilibration buffer
explanatory note: Total material added is evaluated over one or more material addition events in a planned process. The added material may be supplied in a single addition, multiple bolus additions, or continuous feeding. The quantity may be expressed as mass, volume, amount of substance, or another specified material quantity. This characteristic should be distinguished from addition rate or feed rate, which describe the rate of material addition.
first order logic axiom: TotalMaterialAdded(x) → ProcessCharacteristic(x) ∧ ∃p(PlannedProcess(p) ∧ processCharacteristicOf(x,p))
is primitive: true
natural language definition: process characteristic that is the total quantity of a particular material that is added during a particular process
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'total material added' then x is a 'process characteristic' that is the 'process characteristic of' some 'planned process'

vessel volumes per day
type: Class
subclass of: normalized flow rate
example: a perfusion culture operated at 1 VVD, meaning one working volume of medium is exchanged over one day; a 2 L working-volume bioreactor with 2 L of medium exchanged per day, corresponding to 1 VVD; a perfusion process reported as 0.5 VVD when the daily exchanged medium volume is half of the working volume;
abbreviation: VVD
adapted from: https://documents.thermofisher.com/TFS-Assets/BPD/Reference-Materials/perfusion-terminology-white-paper.pdf
explanatory note: VVD is typically intended to represent the total medium exchange normalized by working volume. In some uses, VVD is computed only from the spent-medium outlet flow, while other withdrawals such as sampling, bleed, or additional removal streams are not included. When this narrower accounting is used, the reported VVD can underestimate the true total exchange and can lead to misleading comparisons unless the boundary is made explicit.
first order logic axiom: VesselVolumesPerDay(x) → NormalizedFlowRate(x)
is primitive: true
natural language definition: normalized flow rate whose magnitude is the volume of medium exchanged per day relative to the working volume
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'vessel volumes per day' then x is a 'normalized flow rate'

volumetric flow rate
type: Class
subclass of: flow rate
example: volumetric flow rate of buffer through a chromatography column; volumetric flow rate of permeate through an ultrafiltration membrane; volumetric flow rate of liquid feed through a process line;
adapted from: https://en.wikipedia.org/wiki/Volumetric_flow_rate
first order logic axiom: VolumetricFlowRate(x) → FlowRate(x)
is primitive: true
natural language definition: flow rate whose magnitude is determined by the volume of material transported across the specified surface or boundary per unit of elapsed time
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'volumetric flow rate' then x is a 'flow rate'

volumetric productivity
type: Class
subclass of: manufacturing process productivity
example: monoclonal antibody mass produced per liter of culture working volume per day during a CHO fed-batch process; recombinant protein mass produced per liter of microbial fermentation volume per hour; viral vector genome copies produced per liter of culture volume per day; enzyme activity units produced per liter of culture working volume per hour;
explanatory note: In upstream biopharma manufacturing process volume is typically the culture working volume
first order logic axiom: VolumetricProductivity(x) → ManufacturingProcessProductivity(x)
is primitive: true
natural language definition: manufacturing process productivity whose magnitude is normalized by a specified reference volume of process material
primitive rationale: There are insufficient constructs to create necessary and sufficient conditions.
semi formal natural language axiom: if x is a 'volumetric productivity' then x is a 'manufacturing process productivity'

working volume
type: Class
subclass of: Volume
subclass of: Restriction
  on property: qualityOf
  some values from: Class
    intersection of: BFO_0000040
    intersection of: Restriction
      on property: BFO_0000056
      some values from: PlannedProcess
example: the 120 L working volume of a CHO cell culture in a 250 L bioreactor during a fed-batch cultivation process; the 3 L working volume of buffer in a mixing vessel during buffer preparation;
explanatory note: Working volume is the actual volume of process material present in a vessel during a planned process. It should be distinguished from working volume capacity, which is a capacity of the vessel, and from total vessel volume, which is a geometric volume of the vessel. For example, a bioreactor may have a total vessel volume of 250 L, a working volume capacity of 50–200 L, and a working volume of 120 L during a particular cell cultivation process
first order logic axiom: WorkingVolume(x) → Volume(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m) ∧ ∃p (PlannedProcess(p) ∧ participatesInAtSomeTime(m, p)))
is primitive: true
natural language definition: volume that is a quality of process material and that is the volume occupied by that process material in a vessel during a planned process
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'working volume' then x is a 'volume' that is the 'quality of' some 'material entity' that 'participates in at some time' some 'planned process'

yield per biomass
type: Class
subclass of: planned process yield
example: the yield per biomass of a microbial fermentation calculated as recombinant protein mass produced per gram of biomass formed; the yield per biomass of an E. coli enzyme expression process calculated as enzyme activity units recovered per gram dry cell weight; the yield per biomass of a yeast production process calculated as product mass produced per biomass amount accumulated during cultivation;
first order logic axiom: YieldPerBiomass(x) → PlannedProcessYield(x)
is primitive: true
natural language definition: planned process yield that characterizes the quantity of a specified material output produced in a planned process relative to the quantity of biomass formed in that planned process
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'yield per biomass' then x is a 'planned process yield'

yield per substrate
type: Class
subclass of: planned process yield
subclass of: Restriction
  on property: processCharacteristicOf
  some values from: Class
    intersection of: PlannedProcess
    intersection of: Restriction
      on property: hasInput
      some values from: BFO_0000040
example: the yield per substrate of a microbial fermentation calculated as recombinant protein mass produced per gram of glucose consumed; the yield per substrate of a levansucrase reaction calculated as levan mass produced per gram of sucrose consumed; the yield per substrate of an E. coli enzyme expression process calculated as enzyme activity units recovered per gram of glycerol consumed;
first order logic axiom: YieldPerSubstrate(x) → PlannedProcessYield(x) ∧ ∃p∃m(PlannedProcess(p) ∧ MaterialEntity(m) ∧ processCharacteristicOf(x,p) ∧ hasInput(p,m))
is primitive: true
natural language definition: planned process yield that characterizes the quantity of a specified material output produced in a planned process relative to the quantity of a specified substrate consumed in that planned process
primitive rationale: There are insufficient constructs for creating a set of necessary and sufficient conditions
semi formal natural language axiom: if x is a 'yield per substrate' then x is a 'planned process yield' that is the 'process characteristic of' some 'planned process' that 'has input' some 'material entity'

has performance indicator
type: ObjectProperty
sub property of: topObjectProperty
domain: Class
  union of: Agent
  union of: Organization
  union of: PieceOfEquipment
  union of: PlannedProcess
range: performance indicator
inverse of: is performance indicator of
example: manufacturing organization has performance indicator 12-month on-time delivery percentage; sales organization has performance indicator yearly sales; production culture process has performance indicator product titer; chromatography purification process has performance indicator product recovery
natural language definition: relation between an agent, planned process, organization, or piece of equipment and a performance indicator indicating that measurements of the indicator are used to evaluate the effectiveness of that entity with respect to a particular objective

has process parameter
type: ObjectProperty
sub property of: topObjectProperty
domain: PlannedProcess
range: process parameter
inverse of: is process parameter of
example: cell culture expansion process has process parameter pH; production culture process has process parameter temperature; production phase has process parameter agitation speed
natural language definition: relation between a planned process and a process parameter indicating that the parameter is monitored or controlled during the execution of that planned process
usage note: When this relation is used, it implies that the plan specification (e.g., a rec:RecipeProcessElement or other process plan) that prescribes the planned process must include as a continuant part the corresponding process parameter specification that prescribes the monitored or controlled parameter. In other words, the monitoring or control of a process parameter at execution level must be traceable to a parameter specification at the plan level via bfo:continuantPartOf

is performance indicator of
type: ObjectProperty
sub property of: topObjectProperty
domain: performance indicator
range: Class
  union of: Agent
  union of: Organization
  union of: PieceOfEquipment
  union of: PlannedProcess
example: 12-month on-time delivery percentage is performance indicator of a manufacturing organization; yearly sales is performance indicator of a sales organization; product titer is performance indicator of a production culture process; product recovery is performance indicator of a chromatography purification process
natural language definition: relation between a performance indicator and an agent, planned process, organization, or piece of equipment indicating that measurements of the indicator are used to evaluate the effectiveness of that entity with respect to a particular objective

is process parameter of
type: ObjectProperty
sub property of: topObjectProperty
domain: process parameter
range: PlannedProcess
example: pH is process parameter of a cell culture expansion process; temperature is process parameter of a production culture process; agitation speed is process parameter of a production phase
natural language definition: relation between a process parameter and a planned process indicating that the parameter is monitored or controlled during the execution of that planned process