]> Biopharma Material Ontology This module contains terms and relations enabling representation of material types and their associated properties. Terms for characterizing material usages in internal operation systems are also included (e.g., consumable, process intermediate, final product…). Adlane Rebai, Millipore Sigma Ana Nikolov, OAGi Boonserm Kulvatunyou, NIST Cameron Gibbs, CrownPoint Technologies, LLC Gabriela Henning, NIST Jan Kemper, AstraZeneca Marie-Aude Coutouly, Millipore Sigma Melissa Weller, CrownPoint Technologies, LLC Milos Drobnjakovic, OAGi Stephen J. Granite, CrownPoint Technologies, LLC Stephen Kahmann, CrownPoint Technologies, LLC NIIMBL BD-1 Ontology Group http://opensource.org/licenses/MIT NIIMBL Material Ontology

acidifying agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the acidifying agent role of hydrochloric acid solution used to lower the pH of a buffer; the acidifying agent role of phosphoric acid during phosphate buffer preparation; the acidifying agent role of acetic acid during acetate buffer preparation;

AcidifyingAgentRole(x) → PHAdjustingAgentRole(x)

true

pH adjusting agent role of a material entity when it is used, or planned to be used, to lower pH

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'acidifying agent role' then x is a 'pH adjusting agent role'

alkalizing agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the alkalizing agent role of sodium hydroxide solution used to raise the pH of a buffer; the alkalizing agent role of potassium hydroxide solution during formulation pH adjustment;

AlkalizingAgentRole(x) → PHAdjustingAgentRole(x)

true

pH adjusting agent role of a material entity when it is used, or planned to be used, to raise pH

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'alkalizing agent role' then x is a 'pH adjusting agent role'

alkalinizing agent role

basifying agent role

amount of substance https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ molar amount the molar amount of glucose in a glucose constituent of a cell culture medium; the molar amount of sodium ions in a buffer solution constituent; the molar amount of calcium ions in a media formulation; the molar amount of glucose in a portion of glucose powder

https://www.nist.gov/pml/owm/si-units-amount-substance

AmountOfSubstance(x) → Quality(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m) ∧ ∀p (hasMagnitudeBasisInBearerPart(x, p) → (MaterialEntity(p) ∧ isMadeOfAtSomeTime(m, p))))

true

quality of a material entity that is proportional to the number of elementary entities of a particular kind present in that material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'amount of substance' then x is a 'quality' that is the 'quality of' some 'material entity', and if x 'has magnitude basis in bearer part' some p, then p is a 'material entity' of which that same 'material entity' 'is made of at some time'

antifoaming agent https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Polydimethylsiloxane serving as an antifoam in a mammalian cell culture bioreactor to minimize surface foaming; Silicone-based antifoam used during protein purification to prevent foam buildup in chromatographic buffers

http://purl.obolibrary.org/obo/CHEBI_77973

See expanded definition under the corresponding role class. The term is formalized here as a defined class by referring to its corresponding role class and exists primarily for ontological modeling and implementation convenience.

AntifoamingAgent(x) ↔ MaterialEntity(x) ∧ ∃r(AntifoamingAgentRole(r) ∧ hasRole(x,r))

material entity with an antifoaming agent role

every instance of 'antifoaming agent' is defined as exactly an instance of 'material entity' that 'has role' some 'antifoaming agent role'

antifoaming agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Polydimethylsiloxane serving as an antifoam in a mammalian cell culture bioreactor to minimize surface foaming; Silicone-based antifoam used during protein purification to prevent foam buildup in chromatographic buffers

http://purl.obolibrary.org/obo/CHEBI_77973

This role is typically realized during mixing, aeration, fermentation, or other processing steps where gas–liquid interfaces promote foam generation. Substances bearing this role are often surfactants or hydrophobic agents that disrupt bubble stability and ensure process continuity

AntifoamingAgentRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role of a material entity when it is used, or planned to be used, to reduce or prevent foam formation in a liquid

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'antifoaming agent role' then x is a 'role' that is the 'role of' some 'material entity'

bacterium cell https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ an Escherichia coli cell; a Bacillus subtilis cell; a Pseudomonas aeruginosa cell; a Staphylococcus aureus cell; a Lactobacillus cell; a bacterial cell detected during bioburden testing

https://pubmed.ncbi.nlm.nih.gov/19819658/ and https://www.britannica.com/science/bacteria

BacteriumCell(x) → Cell(x)

true

cell that lacks a membrane-bound nucleus and has ribosomes of the bacterial type

This term is expected to remain primitive. Speciation is out of the scope of IOF and should be utilized if needed from a biological ontology

if x is a 'bacterium cell' then x is a 'cell'

basal culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ MEM (Minimum Essential Medium); DMEM (Dulbecco’s Modified Eagle Medium)

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

See the expanded definition under the corresponding role class. The term is formalized here as a defined class by referring to its corresponding role class and exists primarily for ontological modeling and implementation convenience.

BasalCultureMedium(x) ↔ CultureMedium(x) ∧ ∃f (BasalCultureMediumRole(f) ∧ hasRole(x, f))

culture medium which has the basal culture medium role

every instance of 'basal culture medium' is defined as exactly an instance of 'culture medium' when it 'has role' some 'basal culture medium role'

basal culture medium role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ MEM bearing a basal culture medium role when planned to be supplemented with fetal bovine serum to support robust proliferation of mammalian cells

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

BasalCultureMediumRole(x) → Role(x) ∧ ∃m (CultureMedium(m) ∧ roleOf(x, m)) ∧ ∀p (hasRealization(x, p) → (PlannedProcess(p) ∧ ((∃s (CultureMediumSupplement(s) ∧ hasInput(p, s))) ∨ (∃c (CellCulture(c) ∧ hasParticipantAtSomeTime(p, c))))))

true

role held by a culture medium when it is used or planned to be used either directly in a cell culture process to provide essential nutritional and physicochemical support or together with supplements to prepare a complete culture medium for such a process

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'basal culture medium role' then x is a 'role' that is the 'role of' some 'culture medium', and if x 'has realization' some entity then that entity is a 'planned process' that either 'has input' some 'culture medium supplement' or 'has participant at some time' some 'cell culture'

bioburden https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the bioburden of a raw material lot before use in manufacturing; the bioburden of a process intermediate before sterile filtration; the bioburden of equipment surfaces after cleaning; the bioburden of a water sample from a water system; the bioburden of a packaging component before sterilization

https://www.sigmaaldrich.com/US/en/applications/microbiological-testing/bioburden-testing?srsltid=AfmBOooIv6z3mhn24wCBPWkNZ1d0tqxlOup_y_ and https://www.biophorum.com/download/cvp-case-study-interactive-version/

1) In sterilization and aseptic processing contexts, bioburden is commonly assessed prior to a sterilization or other microbicidal process and is used to characterize the microbial challenge presented to that process 2) This quality refers only to viable microorganisms such as bacteria, yeast, or mold present within or on a material entity. It excludes viruses, endotoxins, and non-viable biological matter, which are represented by separate quality attributes.

Bioburden(x) → RelationalQuality(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m))

true

relational quality of a material entity that is the extent to which viable microorganisms are present in or on the surface of the material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions. In particular located on is still missing

if x is a 'bioburden' then x is a 'relational quality' that is the 'quality of' some 'material entity'

bioproduction supporting function https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ function of Hybridoma Myeloma Cell Culture Media; function of CHO production media; function of HEK293 production medium used for viral vector production

https://www.sciencedirect.com/topics/engineering/production-medium#:~:text=The%20production%20media%20have%20the,cost%20and%20to%20enhance%20yields and https://www.fishersci.com/us/en/browse/90217078/hybridoma-myeloma-cell-culture-media

BioproductionSupportingFunction(x) → SpecializedCultureMediumFunction(x)

true

culture medium specialized function that enables the generation of a target biological product by sustaining cellular activity under production conditions

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'bioproduction supporting function' then x is a 'specialized culture medium function'

buffer solution https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ phosphate buffer used during protein purification; acetate buffer used during chromatography; citrate buffer used in formulation development; Tris buffer used during biochemical processing; HEPES-buffered culture medium; bicarbonate-buffered culture medium under CO₂ control

http://purl.obolibrary.org/obo/NCIT_C70815 and https://www.fda.gov/files/drugs/published/pH-Adjuster-Webinar-Slides.pdf

BufferSolution(x) ↔ Solution(x) ∧ ∃f (BufferingFunction(f) ∧ hasFunction(x, f))

solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid which is resistant to pH changes upon addition of an acidic or basic component

every instance of 'buffer solution' is defined as exactly an instance of 'solution' that 'has function' some 'buffering function'

buffering agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ mixture of sodium phosphate monobasic and dibasic salts playing a buffer role in cell-culture medium to maintain pH near neutrality; combination of Tris base and Tris-HCl playing a buffer role in electrophoretic buffer solution to maintain pH around 8; pair of HEPES and its conjugate acid playing a buffer role in tissue-culture medium to maintain physiological pH; combination of carbon dioxide and sodium bicarbonate playing a buffer role in mammalian cell-culture medium to stabilize pH under CO₂ atmosphere; mixture of histidine and histidine hydrochloride playing a buffer role in monoclonal-antibody formulation to stabilize pH during storage;

http://purl.obolibrary.org/obo/CHEBI_35225

sodium chloride solution adjusting ionic strength but not buffering pH; phenol red acting as a pH indicator rather than stabilizer; pure acetic acid lacking conjugate base and unable to resist pH change; hydrochloric acid solution changing rather than maintaining pH

A buffering agent role inheres in a material entity that serves as the material basis of buffering capacity in a system. The role connects the substance or combination of substances to the capability by which the system resists a change in hydrogen-ion concentration when small amounts of acid or base are added. The role may also be assigned to powders or concentrated materials before they are dissolved, reflecting the planned use of those substances to establish buffering capacity once introduced into a solution.

BufferingAgentRole(x) → Role(x) ∧ ∃m(MaterialEntity(m) ∧ roleOf(x, m) ∧ ((∃s∃b(MixedMaterial(s) ∧ BufferingCapability(b) ∧ hasCapability(s, b) ∧ continuantPartOfAtSomeTime(m, s) ∧ materialBasisOfAtSomeTime(m, b))) ∨ (∃i∃p∃o∃s∃b(InputSpecification(i) ∧ PlanSpecification(p) ∧ continuantPartOfAtAllTimes(i, p) ∧ prescribes(p, o) ∧ PlannedProcess(o) ∧ prescribedBy(m, i) ∧ MixedMaterial(s) ∧ hasSpecifiedOutput(o, s) ∧ BufferingCapability(b) ∧ hasCapability(s, b)))))

true

role of a material entity when it is added or planned to be added to a mixture, typically aqueous, to enable or enhance the mixture's resistance to changes in pH upon the addition of small amounts of acid or base

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'buffering agent role', then x is a 'role' that is the 'role of' some 'material entity' that either is a 'continuant part of at some time' some 'mixed material' and is the 'material basis of at some time' some 'buffering capability' that is a 'capability of' that 'mixed material', or is 'prescribed by' some 'input specification' that is a 'continuant part of at all times' some 'plan specification' that 'prescribes' some 'planned process' that 'has specified output' some 'mixed material' that 'has capability' some 'buffering capability'

buffering capability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the buffering capability of a phosphate buffer during acid addition; the buffering capability of a bicarbonate-buffered cell culture medium under CO₂ control; the buffering capability of a formulation buffer during base addition; the buffering capability of a chromatography buffer during pH adjustment; the buffering capability of a harvest fluid when acidic or basic species are introduced

https://www.med.unc.edu/pharm/sondeklab/wp-content/uploads/sites/868/2018/10/buffers_calbiochem.pdf

Buffering capability is realized when a solution resists pH change in the presence of acid or base material. The acid or base material may be externally added, such as during pH adjustment or titration, or may arise within the system, such as acidic species generated during cell culture metabolism, CO₂ dissolution from culture respiration, or basic species formed through process chemistry. Buffering capability should be distinguished from buffering capacity, which characterizes the extent or strength of this capability.

BufferingCapability(x) → Capability(x) ∧ ∃s (Solution(s) ∧ capabilityOf(x, s))

true

capability of a solution to resist a change in pH when acid or base is added

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'buffering capability' then x is a 'capability' that is the 'capability of' some 'solution'

buffering function https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the buffering function of a phosphate buffer solution prepared for buffer exchange; the buffering function of a Tris buffer solution prepared for a chromatography process; the buffering function of an acetate buffer solution prepared for protein formulation;

BufferingFunction(x) ↔ BufferingCapability(x) ∧ ∃s (Solution(s) ∧ functionOf(x,s))

function of a solution to resist a change in pH when an acid or base is added

every instance of 'buffering function' is exactly an instance of 'buffering capability' that is the 'function of' some 'solution'

bulk density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the bulk density of powdered cell culture medium; the bulk density of granulated medium; the bulk density of chromatography resin beads; the bulk density of an excipient powder lot;

https://en.wikipedia.org/wiki/Bulk_density

The total bulk volume is the volume occupied by the particulate material prior to any intentional compaction, mechanical tapping, or vibration.

BulkDensity(x) → MassDensity(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m) ∧ ∃f (ParticulateForm(f) ∧ hasQuality(m, f)))

true

mass density of a particulate material that is the mass per total bulk volume occupied by the material, where the total bulk volume includes particle volume, pore volume within particles, and void volume between particles

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a 'bulk density' then x is a 'mass density' that is the 'quality of' some 'material entity' that 'has quality' some 'particulate form'

apparent density

caking propensity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the caking propensity of powdered cell culture medium during storage under humid conditions; the caking propensity of a granulated medium during transport; the caking propensity of an excipient powder after exposure to moisture;

https://www.sciencedirect.com/science/article/pii/S0032591017301511 and https://www.sciencedirect.com/science/article/abs/pii/S1004954118308747

Caking propensity is typically realized when a particulate material experiences environmental or mechanical conditions over time, such as during storage, transport, or handling. Conditions such as humidity or moisture exposure, temperature, applied pressure, self-weight consolidation, particle dissolution and recrystallization, electrostatic effects, and particle-particle adhesion can influence whether and how rapidly caking develops. Caking propensity should be distinguished from caked form, which is the material form resulting when caking has occurred, and from flowability, which concerns the capability of a material to flow under a handling or processing context.

CakingPropensity(x) → Disposition(x) ∧ ∃m (MaterialEntity(m) ∧ dispositionOf(x, m) ∧ ∃f (ParticulateForm(f) ∧ hasQuality(m, f)))

true

disposition of a particulate material entity to form persistent lumps, agglomerates, or a coherent solid mass

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'caking propensity' then x is a 'disposition' that is the 'disposition of' some 'material entity' that 'has quality' some 'particulate form'

carbon source role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Role held by glucose as the main carbon source in DMEM (Dulbecco’s Modified Eagle’s Medium) or CD-CHO media; Role held by methanol serving as the carbon source in Pichia pastoris expression systems; role held by protein hydrolysate serving as a carbon-containing nutrient material in culture medium

https://www.thermofisher.com/ba/en/home/references/gibco-cell-culture-basics/cell-culture-environment/culture-media.html and https://clinref.com/data/uploads/books/LehningerBiochemistry6thed.pdf and https://link.springer.com/article/10.1007/s11626-017-0186-6

1) Carbon sources provide the essential carbon that forms the backbone of cellular structures and fuels metabolic energy production. 2) In mammalian-cell culture, glucose is the primary carbon source, supporting both energy generation and biosynthesis. Alternative substrates such as galactose, fructose, or pyruvate may be used to adjust metabolic fluxes or reduce lactate buildup. In microbial and yeast cultures, carbon sources can include glycerol, sucrose, acetate, or methanol, depending on the organism and process objectives. 3) The role may also be borne by complex nutrient materials, such as protein hydrolysates, yeast extract, peptones, or feed mixtures, when they provide carbon-containing constituents used by the organism or cell. 4) The selection and concentration of the carbon source directly affect growth, productivity, and by-product formation in manufacturing processes

CarbonSourceRole(x) → NutrientRole(x)

true

nutrient role held by a material entity that provides carbon used by an organism or cell for biosynthesis, energy generation, or both

This term is expected to remain primitive as the detailed treatment of biochemical processes is outside of the current scope of IOF. Other biological and chemical ontologies should be used for these purposes

if x is a 'carbon source role' then x is a 'nutrient role'

cell https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO-K1 cell; HeLa cell; T cell isolated from peripheral blood; Freshly isolated hepatocyte; Hematopoietic stem cell isolated from bone marrow

http://purl.obolibrary.org/obo/CL_0000000

1) From CL term: The definition of cell is intended to represent all cells, and thus a cell is defined as a material entity and not an anatomical structure, which implies that it is part of an organism (or the entirety of one). 2) In the cell line ontology the term is directly under material entity. However, given the definitional criteria of a plasma membrane and maximal connectedness of cell compartments, the cell has been put under object within the ontology.

Cell(x) → Object(x)

true

object of anatomical origin (part of or deriving from an organism) that has as its parts a maximally connected cell compartment surrounded by a plasma membrane

There are currently insufficient constructs to represent cellular components or cell derivation

if x is a 'cell' then x is an 'object'

cell bank https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a master cell bank used to generate working cell banks; a working cell bank used to inoculate production cultures;

https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-5-d-derivation-and-characterisation-cell-substrates-used-production-biotechnologicalbiological-products-step-5_en.pdf and https://extranet.who.int/prequal/glossary-acronyms/s#:~:text=A%20master%20seed%20lot%20

The container contents of a cell bank are typically cryopreserved.

CellBank(x) → ObjectAggregate(x)

true

object aggregate consisting of containers whose contents are uniform portions derived from a single pool of cells and that are stored under defined conditions as a referenceable source of cells

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'cell bank' then x is an 'object aggregate'

cell count https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the viable cell count of a cell culture sample; the cell count of a cell suspension before seeding; the cell count of a thawed cell vial;

http://purl.allotrope.org/ontologies/quality#AFQ_0000184

CellCount(x) → Count(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → Cell(p))

true

count that is the number of cells that are present as parts of a material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'cell count' then x is a 'count', and if x 'has magnitude basis in bearer part' some p, then p is a 'cell'

cell culture https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ culture broth CHO Suspension Culture in CD-CHO Medium; HEK293 cells growing as an adherent monolayer when cultured in DMEM (Dulbecco's Modified Eagle's Medium) + 10% FBS (Fetal Bovine Serum)

OBI:0001876

In situ cells are observed and studied within their natural tissue context without being cultured or removed, e.g., neurons, alveolar epithelial cells; Post-centrifugation cell pellet; Uninoculated Culture Medium; Glass Slide with Fixed Cells (No Live Media); Tissue Biopsy in PBS Buffer

A cell culture includes the cells in culture, as well as the media and all additives in which the cells are being grown or in which they are stored.

CellCulture(x) → MaterialEntity(x) ∧ ∃y (CultureMedium(y) ∧ hasContinuantPartAtAllTimes(x, y)) ∧ ∃z (CulturedCellPopulation(z) ∧ hasContinuantPartAtAllTimes(x, z))

true

material entity that has cultured cells and the media in which they are being propagated or stored as parts

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'cell culture' then x is a 'material entity' and x 'has continuant part at all times' some 'culture medium' and x 'has continuant part at all times' some 'cultured cell population'

cell culture derived impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the cell culture-derived impurity role of residual insulin from a cell culture medium supplement remaining in a harvested process intermediate; the cell culture-derived impurity role of residual antibiotic from a selection medium remaining in a downstream intermediate; the cell culture-derived impurity role of residual antifoam agent carried from a bioreactor culture into a harvest pool; the cell culture-derived impurity role of residual surfactant from a culture medium additive detected in a process intermediate; the cell culture-derived impurity role of residual inducer used during recombinant protein expression and carried into a clarified harvest; the cell culture-derived impurity role of residual nutrient feed component remaining in a harvested cell culture fluid;

https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf and https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-q11-development-and-manufacture-drug-substances-chemical-entities-and-biotechnological-biological-entities_en.pdf

Cell culture-derived impurity role applies to impurities that originate from acellular materials present in or used to maintain a cell culture, such as media components, media supplements, inducers, antibiotics, surfactants, antifoam agents, selection agents, or other culture additives. These materials may remain in downstream or later manufacturing intermediates after harvest or purification. This role excludes materials originating from the production cells or host cell line itself, such as host cell proteins, host cell DNA, cell debris, or other host-cell-derived material. The term cell culture-derived therefore refers to the culture environment and non-cellular materials present in that environment, not to cells, cell parts, or host-cell molecules.

CellCultureDerivedImpurityRole(x) → ManufacturingProcessRelatedImpurityRole(x)

true

manufacturing process related impurity role held by a material entity that originates from an acellular material component of a cell culture

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'cell culture derived impurity role' then x is a 'manufacturing process related impurity role'

cell density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the total cell density of a bioreactor culture sample; the viable cell density of a CHO cell culture during production; the dead cell density of a stressed culture sample after viability analysis;

http://purl.allotrope.org/ontologies/quality#AFQ_0000181

Cell density is commonly reported as cells per unit volume (e.g. cells/mL) or cells per unit area (e.g. cells/cm²), depending on how the cell population is distributed in the material entity being studied. It characterizes how many cells occupy a specified portion of material space and is an important parameter for interpreting cellular behavior such as growth, viability, differentiation, gene expression, and responses to environmental conditions. In practice, cell density may be obtained by direct or automated counting methods or indirectly from surrogate readouts such as optical density at 600 nm (OD600).

CellDensity(x) → NumberDensity(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → Cell(p))

true

number density that is the number of cells per unit size

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a 'cell density' then x is a 'number density', and if x 'has magnitude basis in bearer part' some p, then p is a 'cell'

cell line https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ HeLa cells; HEK293 cells; Vero cells

http://purl.obolibrary.org/obo/CLO_0000031 and https://www.fda.gov/media/78428/download

1) A cell line is typically stored in a cell bank and used to support consistent and reproducible performance across experimental or manufacturing contexts. 2) The term excludes freshly isolated or short-lived primary cultures. 3) Genetic stability and homogeneity are relative to the characteristics by which the cell line is established and maintained and do not imply complete genetic identity among all cells or the absence of genetic or phenotypic change during continued propagation.

CellLine(x) → CulturedCellPopulation(x)

true

cultured cell population that is derived from a primary cell source and that has been propagated through repeated subculture under defined conditions, resulting in a genetically stable and homogeneous population of cells with a shared propagation history

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'cell line' then x is a 'cultured cell population'

cell line lineage https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ cell line history HEK293 history: derived from human embryonic kidney cells transfected with adenovirus 5 DNA selected for stable growth in culture;

CLO:0000171

The cell line lineage may include the original cell type from a tissue and organism that derives the cell line cell. It may also include the cell line passage and cell culturing information.

CellLineLineage(x) ↔ History(x) ∧ ∃y(CellLine(y) ∧ historyOf(x, y))

history of the development of a cell line

every instance of 'cell line lineage' is defined as exactly an instance of 'history' that 'is history of' some 'cell line'

cell population https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO Cell Line; CD4+ T cell population that have been obtained from a mixed cell suspension using fluorescence-activated cell sorting (FACS); Red blood cell pellet; freshly isolated hepatocytes from mouse liver

CellPopulation(x) ↔ ObjectAggregate(x) ∧ ∃y(Cell(y) ∧ hasMemberPartAtSomeTime(x, y)) ∧ ∀z(hasMemberPartAtSomeTime(x, z) → Cell(z))

object aggregate which only has cells as its member parts

every instance of 'cell population' is defined as exactly an instance of 'object aggregate' that 'has member part at some time' some 'cell' and 'has member part at some time' only 'cell'

cell proliferation supporting function https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ function of Human-Mesenchymal-XF-Expansion-Medium; function of T cell expansion medium containing cytokines;

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

chemically defined production medium optimized for antibody yield may maintain cell viability but does not primarily function as a proliferation medium

CellProliferationSupportingFunction(x) → SpecializedCultureMediumFunction(x)

true

specialized culture medium function that supports cell division and maintenance of cell viability during expansion culture by providing appropriate nutrients and culture-supporting physicochemical properties

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'cell proliferation supporting function' then x is a 'specialized culture medium function'

cell substrate derived impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the cell substrate-derived impurity role of host cell protein remaining in a monoclonal antibody process intermediate; the cell substrate-derived impurity role of residual host cell DNA detected in a drug substance intermediate; the cell substrate-derived impurity role of host cell RNA remaining after harvest clarification;

Cell-derived impurity role applies to impurities originating from cells used in manufacturing. Examples include host cell proteins, host cell DNA, host cell RNA, cell debris, host-cell-derived lipids, or other material released from or derived from production cells. This role should be distinguished from cell culture-derived impurity role, which applies to impurities originating from non-cellular materials present in or added to the culture environment, such as media components, nutrient feeds, supplements, inducers, antibiotics, surfactants, or antifoam agents.

CellSubstrateDerivedImpurityRole(x) → ManufacturingProcessRelatedImpurityRole(x)

true

manufacturing process related impurity role held by a material entity that originates from cells used in a manufacturing process

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'cell substrate derived impurity role' then x is a 'manufacturing process related impurity role'

cell viability ratio https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the cell viability ratio of a CHO cell culture reported as 95% viable during production; the cell viability ratio of a thawed cell suspension after recovery; the cell viability ratio of a seed train culture before inoculation; the cell viability ratio of a T cell preparation assessed by FACS using a viability dye;

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cell-viability

CellViabilityRatio(x) → RelativeAbundance(x)

true

relative abundance that is the number of viable cells in a cell population relative to the total number of cells in that population

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'cell viability ratio' then x is a 'relative abundance'

chemical substance material https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a portion of water; a lot of Water for Injection; a sodium chloride raw material; a glucose powder; an L-glutamine powder; portion of CO2 gas; portion of crystalline sucrose

http://purl.allotrope.org/ontologies/material#AFM_0001060 and http://purl.obolibrary.org/obo/CHEBI_60003

a 70 percent ethanol solution; phosphate-buffered saline; a chemically defined culture medium; a glucose powder blend containing compositionally intentional excipients; air; polymer composite

A chemical substance material is a material entity whose identity is based primarily on being made of molecular entities of one chemically specified kind. The term does not require absolute purity. Minor impurities may include trace contaminants, residual water, dissolved gases, degradation products, residual process chemicals, or other low-level material present below the level at which the material is treated as a mixed material for the applicable modeling purpose. Materials whose identity depends on the joint presence of multiple compositionally relevant constituents, such as solutions, culture media, buffers, formulations, and hydrolysates, should be modeled as mixed materials.

ChemicalSubstanceMaterial(x) → MaterialEntity(x) ∧ ∃m (MolecularEntity(m) ∧ isMadeOfAtAllTimes(x, m))

true

material entity that is made primarily of one kind of molecular entity, allowing for minor impurities

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a ‘chemical substance material’ then x is a ‘material entity’ that ‘is made of at all times’ some ‘molecular entity’

chemically defined culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ ExpiCHO Expression Medium is chemically defined, serum-free, used in high-density fed-batch processes

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

Media with plasma-derived transferrin (without purity specification) is not strictly chemically defined unless concentration is characterized

Chemically defined media (CDM) are culture media composed only of pure, quantified ingredients of known chemical identity and concentration. They exclude animal-derived serum and complex additives such as yeastolate, peptones, or hydrolysates. Recombinant proteins (e.g., insulin, transferrin) may be included provided their identity and concentration are specified. CDMs improve control, reproducibility, and lot-to-lot consistency, simplify downstream purification, and enhance comparability between experiments or production runs. In biopharmaceutical manufacturing, they are favored for reducing regulatory concerns associated with serum and undefined additives.

ChemicallyDefinedCultureMedium(x) → SerumFreeCultureMedium(x)

true

serum free culture medium in which each component and its concentration are known and reproducible, and that excludes undefined components such as serum, extracts, or hydrolysates

There are insufficient constructs available to create a set of necessary and sufficient conditions.

if x is a 'chemically defined culture medium' then x is a 'serum free culture medium'

cloned cell line https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO DG44 clone 5F7 – a clonal derivative of CHO DG44 cells selected for high monoclonal antibody productivity; Jurkat E6-1 – a cloned subline of Jurkat cells used in T cell signaling research

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cell-clone#:~:text=Clone%20of%20cells%20is%20a,ignored%20that%20may%20be%20different and http://purl.obolibrary.org/obo/CLO_0000177

1) A cloned cell line consists of cells that are expected to be genetically identical with respect to antigen recognition, gene sequence, and key phenotypic traits. It represents a uniform lineage of cells with shared ancestry and consistent functional characteristics. 2) Regulatory standards in biologics require proof of monoclonality for a production cell line. This implies that it originates from a single progenitor cell, regardless of whether one calls it a clone or a line. In practice, a clone is the starting point for development: once selected and scaled, it becomes a permanent cell line with specific attributes used for product manufacture. 3) FDA considers monoclonality essential: production cell lines must originate from a single progenitor cell to ensure consistent and safe product characteristics. Each clone selected after transfection or genetic manipulation is treated as a distinct cell line, subject to full characterization (identity, purity, adventitious agent testing, etc.)

ClonedCellLine(x) → CellLine(x)

true

cell line that originates from a single ancestral cell

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'cloned cell line' then x is a 'cell line'

compendial grade classifier https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ USP grade classification of a sodium chloride raw material lot; Ph. Eur. grade classification of a buffer component; compendial grade classification of an excipient lot against an applicable USP monograph; compendial grade classification of water for injection against an applicable pharmacopeial monograph;

https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/generalNoticesandRequirementsFinal.pdf

A compendial grade classifier is used when the meaning of the grade is anchored in a pharmacopeial monograph rather than only in a supplier datasheet or internal specification. In this setting, compendial denotes that the material is associated with an official pharmacopeial standard and is expected to meet the monograph's stated tests and acceptance criteria. Examples of pharmacopeias include USP and Ph. Eur.

CompendialGradeClassifier(x) → MaterialGradeClassifier(x)

true

material grade classifier that classifies a material entity as conforming to the requirements stated in an applicable pharmacopeial monograph

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'compendial grade classifier' then x is a 'material grade classifier'

complete culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ DMEM (Dulbecco’s Modified Eagle’s Medium) + 10 % FBS (Fetal Bovine Serum)

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

CompleteCultureMedium(x) ↔ CultureMedium(x) ∧ ∃f (CompleteCultureMediumRole(f) ∧ hasRole(x, f))

culture medium which has the complete culture medium role

every instance of 'complete culture medium' is defined as exactly an instance of 'culture medium' when it 'has role' some 'complete culture medium role'

complete culture medium role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ DMEM (Dulbecco’s Modified Eagle’s Medium) supplemented with 10% fetal bovine serum bearing a complete culture medium role when planned for direct use in a mammalian cell culture process

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

A culture medium bearing this role may be supplied as a complete formulation or prepared in advance by supplementing a basal culture medium with materials such as serum or growth factors. In either case, it requires no further supplementation before direct use in the specified cell culture process. The addition of culture feeds later in the process does not alter its classification as a complete culture medium.

CompleteCultureMediumRole(x) → Role(x) ∧ ∃m (CultureMedium(m) ∧ roleOf(x, m)) ∧ ∀p (hasRealization(x, p) → (PlannedProcess(p) ∧ ∃c (CellCulture(c) ∧ hasParticipantAtSomeTime(p, c))))

true

role held by a culture medium when it is used or planned for direct use in a cell culture process to meet the full set of nutritional, biological, and physicochemical requirements specified for that process without requiring prior supplementation

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'complete culture medium role' then x is a 'role' that is the 'role of' some 'culture medium', and if x 'has realization' some entity then that entity is a 'planned process' that 'has participant at some time' some 'cell culture'

concentration https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ mass concentration of glucose in a cell culture medium; the molar concentration of sodium chloride in a buffer solution; the mass concentration of dissolved oxygen in culture fluid; the mass concentration of protein in a drug substance solution; the molar concentration of carbon dioxide in incubator air

http://purl.obolibrary.org/obo/PATO_0000033 and https://pubs.rsc.org/ay/article/12/41/5010/673606/Units-and-quantities-for-analytical-chemistry

Concentration(x) → RelationalQuality(x) ∧ ∃m (MixedMaterial(m) ∧ qualityOf(x, m) ∧ ∀c (hasMagnitudeBasisInBearerPart(x, c) → (MaterialEntity(c) ∧ isMadeOfAtSomeTime(m, c))))

true

relational quality of a mixture that is the amount of substance or number or mass or volume of a specified constituent of the mixture per unit volume of that mixture

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'concentration' then x is a 'relational quality' that is the 'quality of' some 'mixed material', and if x 'has magnitude basis in bearer part' some c, then c is a 'material entity' of which that same 'mixed material' 'is made of at some time'

contaminant role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the contaminant role of mycoplasma adventitiously introduced into a mammalian cell culture; the contaminant role of an adventitious virus introduced through contaminated biological raw material; the contaminant role of bacterial cells introduced into a buffer preparation during manufacturing; the contaminant role of environmental particulate matter introduced during an open handling step of a manufacturing process

https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf

1) Manufacturing contaminants are adventitiously introduced materials that were not intended to be present in the manufacturing process, and in biopharmaceutical manufacturing they include chemical or biochemical materials (e.g., microbial proteases) and microbial species. 2) This role is intended to distinguish contaminants from process-associated impurities that arise from planned or inherent aspects of executing the intended process. 3) Regulators expect manufacturing programs to prioritize avoidance, or controlled removal to meet drug substance or drug product specifications, using appropriate in-process acceptance criteria or measurable action thresholds for the affected material stream, while recognizing that adventitious viral or mycoplasma contamination is not managed by allowable-range action limits, and instead requires control strategies guided by dedicated ICH viral-safety and cell-substrate characterization guidance, as part of validated contamination-prevention or mitigation safeguards

ContaminantRole(x) → MaterialImpurityRole(x)

true

material impurity role held by a material entity when it is adventitiously introduced during a manufacturing process

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'contaminant role' then x is a 'material impurity role'

cryoprotective agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ role held by Dimethyl sulfoxide (DMSO) added to freezing medium for cell preservation; role held by a glycerol solution protecting microbial cultures during storage at low temperatures

http://id.nlm.nih.gov/mesh/D003451 and http://purl.obolibrary.org/obo/NCIT_C53306

1) This role is realized through physicochemical effects that help preserve molecular, cellular, or material integrity during cooling, freezing, frozen storage, or thawing. These effects may include reducing formation of large ice crystals, stabilizing hydration state, maintaining osmotic balance, and limiting cold-induced or thaw-induced damage. 2) The protected material may be present in a solution, suspension, culture medium, formulation, cryopreservation medium, or other relevant material context. 3) The role may be borne by a single substance or by a formulated mixture, such as a cryoprotective solution

CryoprotectiveAgentRole(x) → ProtectiveAgentRole(x)

true

protective agent role of a material entity when it is used, or planned to be used, to protect one or more other material entities from damage during cooling, freezing, frozen storage, or thawing

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'cryoprotective agent role' then x is a 'protective agent role'

culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ DMEM (Dulbecco’s Modified Eagle’s Medium); LB (Lysogeny Broth) agar; AMBIC (Advanced Mammalian Biomanufacturing Innovation Center) medium

https://pmc.ncbi.nlm.nih.gov/articles/PMC7417654/pdf/fbioe-08-00911.pdf and https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/microbiological-testing/microbial-culture-media-preparation/types-of-media-in-microbiology?srsltid=AfmBOopAW7ApixpJ8J-96cmEfgfSiT8dX8wszs06BrclD3tYImJkEcYV

1) “Specific metabolic activity” refers to those metabolic processes that are intentionally supported or induced by the medium in a manufacturing or experimental context. This includes the synthesis and secretion of desired biomolecules (e.g., recombinant proteins, metabolites) or the replication and viability of cells when the cells themselves are the intended product. It excludes background or non-targeted metabolic processes such as basal energy maintenance or stress responses not relevant to the production goal. 2) In the context of biomanufacturing, “specific metabolic activity” typically refers to the set of biochemical processes carried out by microorganisms or cells that result in the synthesis, modification, and/or secretion of desired biological products. This includes processes such as the expression of recombinant proteins (e.g., monoclonal antibodies, enzymes), production of metabolites (e.g., amino acids, organic acids, antibiotics), or replication of the cells themselves when they are the product. These activities require the uptake and transformation of nutrients and are influenced by the composition and physicochemical properties of the culture medium. 3) Some types of culture media also include selection agents or antibiotics to suppress the growth of unwanted or contaminating organisms.

CultureMedium(x) → MixedMaterial(x)

true

mixed material that is a liquid, semi-solid or solid formulation that provides essential nutrients (such as carbon, nitrogen, vitamins, and minerals) and controlled physicochemical conditions (such as pH and osmotic balance) required for the growth, maintenance, or specific metabolic activity of microorganisms or cells

This term is expected to remain primitive because it encompasses a broad set of media that are used for different purposes and have different compositions

if x is a 'culture medium' then x is a 'mixed material'

culture medium supplement https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Albumin solution is a media supplement when added to serum-free medium to stabilize cells; ITS+3 Liquid Media Supplement (100×), a defined mixture of insulin, human transferrin, sodium selenite, linoleic acid, oleic acid added to serum-free medium to support viability and specialized functions;

https://www.labome.com/method/Cell-Culture-Media-A-Review.html and https://www.thermofisher.com/rs/en/home/life-science/cell-culture/mammalian-cell-culture/media-supplements.html

CultureMediumSupplement(x) ↔ MaterialEntity(x) ∧ ∃r(CultureMediumSupplementRole(r) ∧ hasRole(x, r))

material entity that has a culture medium supplement role

every instance of 'culture medium supplement' is defined as exactly an instance of 'material entity' that 'has role' some 'culture medium supplement role'

culture medium supplement role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Albumin stock solution bearing a media supplement role when added to serum-free medium to stabilize cells; ITS+3 Liquid Media Supplement (100×), a defined mixture of insulin, human transferrin, sodium selenite, linoleic acid, oleic acid bearing a media supplement role when added to serum-free medium to support viability and specialized functions;

https://www.labome.com/method/Cell-Culture-Media-A-Review.html and https://www.thermofisher.com/rs/en/home/life-science/cell-culture/mammalian-cell-culture/media-supplements.html

Albumin used as a blocking agent in immunoassays; Dulbecco’s Modified Eagle Medium (DMEM), a complete culture medium formulation providing baseline nutrients, is a culture medium and not a media supplement; Sterile water used as a solvent to reconstitute culture medium powder

1) This role is context-dependent: a substance only counts as a media supplement when it is actually used or planned to be used to supplement culture media. The same chemical could serve other purposes in other settings (for example, insulin as a therapeutic drug). However, many commercial products (such as ITS mixes, lipid concentrates, or amino acid solutions) are specifically formulated and sold for use as media supplements. In practice, these preparations almost always bear a media supplement role. 2) Role may be held by single components and their solutions (such as insulin, transferrin, or glutamine) or prepared mixtures supplied as concentrated supplement solutions (e.g., ITS+3, MEM non-essential amino acids). 3) Media supplements are distinct from the medium itself (basal/complete formulations are not “supplements”). A component that is part of a basal recipe does not bear this role but a component added on top of a basal medium does. 4) Media supplements are separate from nutrient feeds and the additions during cultivation. When the purpose is to replenish depleted nutrients during cultivation the nutrient feed role should be used instead.

CultureMediumSupplementRole(x) → MaterialComponentRole(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m) ∧ ((∃c (CultureMedium(c) ∧ componentPartOfAtAllTimes(m, c))) ∨ ∃i∃p∃q (InputSpecification(i) ∧ prescribedBy(m, i) ∧ PlanSpecification(p) ∧ continuantPartOfAtAllTimes(i, p) ∧ prescribes(p, q) ∧ PlannedProcess(q) ∧ ∃c (CultureMedium(c) ∧ hasParticipantAtSomeTime(q, c)))))

true

material component role held by a material entity when it is added or planned to be added to culture media to enrich or modify the medium composition or functional properties

There are insufficient constructs to create necessary and sufficient conditions

if x is a 'culture medium supplement role' then x is a 'material component role' that is the 'role of' some 'material entity' that either is a 'component part of at all times' some 'culture medium', or is 'prescribed by' some 'input specification' that is a 'continuant part of at all times' some 'plan specification' that 'prescribes' some 'planned process' that 'has participant at some time' some 'culture medium'

culture preservation function https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ function of cryopreservation medium to maintain cell viability under cryogenic conditions

https://www.thermofisher.com/search/browse/category/us/en/90217066

CulturePreservationFunction(x) → SpecializedCultureMediumFunction(x)

true

culture medium specialized function that maintains cell viability and structural integrity during storage and transport by providing physicochemical conditions and protective components that minimize cellular stress under refrigerated or cryogenic conditions

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'culture preservation function' then x is a 'specialized culture medium function'

cultured cell https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO-K1 cell; HeLa cell

https://www.thermofisher.com/rs/en/home/references/gibco-cell-culture-basics/introduction-to-cell-culture.html and http://purl.obolibrary.org/obo/CL_0000010

Freshly isolated hepatocyte; Hematopoietic stem cell isolated from bone marrow

1) Cultured cells are typically immortalized, meaning they retain the capacity to proliferate indefinitely under suitable growth conditions; in contrast, primary cells such as those directly isolated from a patient without genetic or oncogenic modification undergo a limited number of mitotic divisions before entering senescence or undergoing cell death 2) A blurred line would be the case of the CAR-T cell therapy situation where the cells are often taken directly from the patient, modified (not immortalized), expanded in a bioreactor and then infused back into the patient. In this case, CAR-T cells are still considered cultured cells because they are subjected to ex vivo cultivation under controlled, artificial conditions. After being isolated from a patient (typically as primary T cells), they are genetically modified and then expanded in bioreactors or culture vessels using defined media, gas control, and temperature regulation. Although they are not immortalized, they undergo proliferation outside their native environment. This fulfills the defining criteria of a cultured cell as one that grows in an artificial, controlled setting. Their classification as cultured reflects the environmental and procedural context, not the permanence or origin of the cell line.

CulturedCell(x) → Cell(x)

true

cell that is grown, maintained, or adapted to grow in a controlled artificial environment that supports its survival and proliferation

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'cultured cell' then x is a 'cell'

cultured cell population https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ population of CHO-K1 cells; population of HeLa cells

OBI:0100060

CulturedCellPopulation(x) ↔ CellPopulation(x) ∧ ∃y(CulturedCell(y) ∧ hasMemberPartAtSomeTime(x, y)) ∧ ∀z(hasMemberPartAtSomeTime(x, z) → CulturedCell(z))

cell population which only has cultured cells as its member parts

every instance of 'cultured cell population' is defined as exactly an instance of 'cell population' that 'has member part at some time' some 'cultured cell' and 'has member part at some time' only 'cultured cell'

dead https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO cell classified as dead after trypan blue staining; a T cell classified as dead in a FACS assay using propidium iodide staining; a microbial cell killed by heat stress; a thawed cell that fails a viability dye exclusion assay;

http://purl.obolibrary.org/obo/PATO_0001422

Dead(x) → ViabilityStatus(x)

true

viability status of a biological material entity that has irreversibly ceased to maintain the biological processes characteristic of life

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is 'dead' then x is a 'viability status'

dead cell count https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the dead cell count of a cell suspension determined during viability analysis; the dead cell count of a thawed cell stock assessed after trypan blue staining; the dead cell count of a stressed cell culture sample used in cell death analysis;

http://purl.allotrope.org/ontologies/quality#AFQ_0000187

DeadCellCount(x) → CellCount(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (Cell(p) ∧ ∃d(Dead(d) ∧ hasQuality(p,d))))

true

cell count that is the number of dead cells that are present as parts of a material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a ‘dead cell count’ then x is a ‘cell count’, and if x ‘has magnitude basis in bearer part’ some p, then p is a ‘cell’ that ‘has quality’ some ‘dead’

dead cell density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the dead cell density of a stressed CHO cell culture sample after viability analysis; the dead cell density of a bioreactor culture sample reported by an automated cell counter; the dead cell density of a thawed cell suspension after trypan blue staining; the dead cell density of a production culture sample during late-stage decline; the dead cell density of a cell suspension after exposure to cytotoxic conditions

http://purl.allotrope.org/ontologies/quality#AFQ_0000361

DeadCellDensity(x) → CellDensity(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (Cell(p) ∧ ∃d(Dead(d) ∧ hasQuality(p,d))))

true

cell density that is the number of dead cells per unit size

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a ‘dead cell density’ then x is a ‘cell density’, and if x ‘has magnitude basis in bearer part’ some p, then p is a ‘cell’ that ‘has quality’ some ‘dead’

dead cell population https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the subpopulation of propidium iodide-positive CHO cells identified by flow cytometry within a cell culture; the population of trypan blue-positive cells counted in a bioreactor sample during a cell viability measurement process; the population of nonviable mammalian cells separated from a mixed cell population by fluorescence-activated cell sorting using a membrane-integrity viability stain;

DeadCellPopulation(x) ↔ CellPopulation(x) ∧ ∃y(Cell(y) ∧ ∃q(Dead(q) ∧ hasQuality(y, q)) ∧ hasMemberPartAtSomeTime(x, y)) ∧ ∀z(hasMemberPartAtSomeTime(x, z) → (Cell(z) ∧ ∃r(Dead(r) ∧ hasQuality(z, r))))

cell population consisting of only dead cells

every instance of 'dead cell population' is defined as exactly an instance of 'cell population' that 'has member part at some time' some ('cell' that 'has quality' some 'dead') and 'has member part at some time' only ('cell' that 'has quality' some 'dead')

dissolution role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a sodium chloride portion bearing a dissolution role that is realized in a buffer preparation process having a sodium chloride solution as specified output; a sucrose portion bearing a dissolution role that is realized in a formulation preparation process having an aqueous sucrose solution as specified output

http://purl.allotrope.org/ontologies/role#AFRL_0000274

DissolutionRole(x) → Role(x) ∧ ∀y(hasRealization(x, y) → (Process(y) ∧ ∃z(Solution(z) ∧ hasOutput(y, z))))

true

role held by a material entity that is realized in a dissolution process in which it participates in forming a solution

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'dissolution role', then x is a 'role' and every y that is a 'realization of' x is a 'process' that 'has output' some 'solution'

dissolved oxygen saturation ratio https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the dissolved oxygen saturation ratio of cell culture medium in a production bioreactor at 37 °C; the dissolved oxygen saturation ratio of a seed train culture during aeration control; the dissolved oxygen saturation ratio of medium equilibrated with air before inoculation;

The dissolved oxygen saturation concentration (and therefore the dissolved oxygen saturation ratio) is condition-dependent, varying with temperature, salinity (or ionic strength), total pressure, and the oxygen partial pressure in the gas phase in contact with the liquid. In bioprocessing practice, “100% DO” is commonly defined as equilibrium with air at approximately 21% O₂ (at the prevailing total pressure), rather than equilibrium with pure oxygen, unless otherwise specified.

DissolvedOxygenSaturationRatio(x) → SolutionSaturationRatio(x) ∧ ∃s∃l (Solution(s) ∧ qualityOf(x, s) ∧ LiquidAggregateState(l) ∧ hasQuality(s, l) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (DioxygenMolecule(p) ∧ isMadeOfAtSomeTime(s,p))))

true

solution saturation ratio that is the dissolved oxygen concentration in a liquid solution relative to the dissolved oxygen saturation concentration in that liquid solution

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'dissolved oxygen saturation ratio' then x is a 'solution saturation ratio' that is the 'quality of' some 'solution' that 'has quality' some 'liquid aggregate state', and if x 'has magnitude basis in bearer part' some p, then p is a 'dioxygen molecule' of which that same 'solution' 'is made of at some time'

downstream derived impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the downstream-derived impurity role of residual Protein A ligand leached from chromatography resin into a drug substance intermediate; the downstream-derived impurity role of chromatography resin leachable material detected in an elution pool; the downstream-derived impurity role of filter-derived particulate matter introduced during sterile filtration; the downstream-derived impurity role of a filter-derived organic leachable detected in a formulation intermediate; the downstream-derived impurity role of residual low-pH viral inactivation reagent carried into a neutralized process intermediate;

https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf

DownstreamDerivedImpurityRole(x) → ManufacturingProcessRelatedImpurityRole(x)

true

manufacturing process related impurity role held by a material entity that originates from a raw material, production consumable, or equipment used in a downstream manufacturing process

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'downstream derived impurity role' then x is a 'manufacturing process related impurity role'

dusting propensity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the dusting propensity of powdered cell culture medium during weighing; the dusting propensity of a granulated medium during transfer; the dusting propensity of an excipient powder during dispensing;

DustingPropensity(x) → Disposition(x) ∧ ∃m (MaterialEntity(m) ∧ dispositionOf(x, m) ∧ ∃f (ParticulateForm(f) ∧ hasQuality(m, f)))

true

disposition of a particulate material entity to generate airborne particulate matter during handling or processing

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'dusting propensity' then x is a 'disposition' that is the 'disposition of' some 'material entity' that 'has quality' some 'particulate form'

emulsion propensity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the emulsion propensity of an oil-containing process intermediate when mixed with an aqueous buffer during liquid-liquid extraction; the emulsion propensity of a protein formulation containing surfactant when subjected to vigorous agitation;

EmulsionPropensity(x) → Disposition(x) ∧ ∃m (MaterialEntity(m) ∧ dispositionOf(x, m))

true

disposition of a material entity to form an emulsion

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'emulsion propensity' then x is a 'disposition' that is the 'disposition of' some 'material entity'

energy substrate role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ role held by glucose serving as the main energy substrate in DMEM (Dulbecco’s Modified Eagle’s Medium) or RPMI 1640 cell-culture media; role held by glutamine acting as both an energy and nitrogen source in chemically defined CHO-cell feeds; role held by glycerol used as an energy substrate in E. coli fermentation media

https://clinref.com/data/uploads/books/LehningerBiochemistry6thed.pdf and https://aiche.onlinelibrary.wiley.com/doi/10.1021/bp00036a010 and https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/energy-metabolism

In manufacturing and culture systems, glucose and glutamine are the most common energy substrates supporting mammalian cell growth and productivity. Depending on process conditions, other compounds such as lactate, pyruvate, or specific amino acids may also serve as energy sources. The type and concentration of energy substrates influence cell metabolism, product quality, and process performance, making their control a key part of medium and feed design.

EnergySubstrateRole(x) → NutrientRole(x)

true

nutrient role held by a material entity that is metabolized in cellular pathways to generate adenosine triphosphate, reducing equivalents, or other forms of metabolic energy required for growth, maintenance, or biosynthesis

if x is an 'energy substrate role' then x is a 'nutrient role'

equilibrium saturation concentration https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the equilibrium saturation concentration of sodium chloride in water at 20 °C; the equilibrium saturation concentration of glucose in aqueous solution at 25 °C; the equilibrium saturation concentration of dissolved oxygen in culture medium at 37 °C under a defined oxygen partial pressure; the equilibrium saturation concentration of carbon dioxide in buffer at pH 7.2 under 5% CO₂;

https://doi.usp.org/USPNF/USPNF_M2248_03_01.html and https://goldbook.iupac.org/terms/view/S05740

Equilibrium solubility is the saturation limit at thermodynamic equilibrium: the greatest amount of a solute that can remain dissolved under specified conditions while coexisting in equilibrium with a separate phase of that solute (e.g., a solid/crystalline phase, precipitate, separate liquid phase, or gas phase). The value depends on the stated conditions, including temperature, pressure, and solvent composition, and in many practical systems also depends on pH, ionic strength, and the presence of other solutes or additives. Equilibrium solubility can be reported in multiple composition forms (e.g., molarity, molality, mass concentration, mass fraction, mole fraction), provided the solute, solvent, and equilibrium conditions are specified.

EquilibriumSaturationConcentration(x) → SolutionSaturationConcentration(x)

true

solution saturation concentration of a particular solute at thermodynamic equilibrium

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'equilibrium saturation concentration' then x is a 'solution saturation concentration'

expansion culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Human-Mesenchymal-XF-Expansion-Medium

https://www.thermofisher.com/rs/en/home/references/gibco-cell-culture-basics/cell-culture-environment/culture-media.html and https://www.labome.com/method/Cell-Culture-Media-A-Review.html

chemically defined production medium optimized for antibody yield may maintain cell viability but does not primarily function as a proliferation medium

ExpansionCultureMedium(x) ↔ SpecializedCultureMedium(x) ∧ ∃f (CellProliferationSupportingFunction(f) ∧ hasFunction(x, f))

specialized culture medium that has a cell proliferation supporting function

every instance of 'expansion culture medium' is defined as exactly an instance of 'specialized culture medium' when it 'has function' some 'cell proliferation supporting function'

extractable and leachable impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the extractable and leachable impurity role of a plasticizer extracted from single-use tubing during an extractables study; the extractable and leachable impurity role of an antioxidant degradation product leached from a polymer bag into a process intermediate; the extractable and leachable impurity role of silicone oil transferred from a syringe component into a drug product; the extractable and leachable impurity role of a rubber stopper-derived compound detected in a filled vial during storage;

https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-q3e-guideline-extractables-leachables_en.pdf

1) This role groups cases commonly termed extractables and leachables: Extractables: material entities intentionally extracted from manufacturing components/systems, packaging components, or delivery device components under specified laboratory test conditions; often treated as potential leachables for a given target material and use scenario. Leachables: material entities that migrate from manufacturing components/systems, packaging components, or delivery device components into a target material under established conditions of manufacture and/or labeled storage conditions (or, more generally, established handling/transport/use conditions). 2) “Artifact that contacts the target material” includes, for example, containers/closures, bags, tubing, filters, seals/gaskets, connectors, pumps, and relevant equipment surfaces.

ExtractableAndLeachableImpurityRole(x) → MaterialImpurityRole(x)

true

material impurity role held by a material entity in virtue of that material entity being present in a target material as a result of transfer from an artifact that contacts the target material

There are insufficient constructs to create necessary and sufficient conditions.

if x is an 'extractable and leachable impurity role' then x is a 'material impurity role'

filterability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the filterability of a clarified harvest feed before sterile filtration; the filterability of a cell culture harvest containing residual cell debris; the filterability of a protein formulation containing aggregates

https://www.sciencedirect.com/topics/chemistry/filterability and https://www.cytivalifesciences.com/en/us/insights/how-to-run-a-filterability-test-for-bioprocess-development

1) Filterability is realized in filtration and concerns the tendency of a fluid-solid material to continue passing through a filtration medium rather than rapidly forming deposits that reduce permeability or cause plugging. 2) The bearer can be a fluid material entity containing suspended solids, with slurries and suspensions being common examples. Filterability can vary with the amount and character of suspended solids, properties of the continuous phase, and the filtration medium used. 3) Practical indications of poor filterability include early blockage, marked decline in throughput, rapid pressure increase, or rapid increase in filtration resistance during filtration.

Filterability(x) → Capability(x) ∧ ∃m (MaterialEntity(m) ∧ capabilityOf(x, m) ∧ ∃s (FluidAggregateState(s) ∧ hasQuality(m, s)))

true

capability of a fluid to pass through a filtration medium without undue blockage or loss of permeability

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'filterability' then x is a 'capability' that is the 'capability of' some 'material entity' that 'has quality' some 'fluid aggregate state'

flowability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the flowability of powdered cell culture medium during hopper discharge; the flowability of granular medium during transfer to a mixing vessel; the flowability of an excipient powder during tablet manufacturing; the flowability of chromatography resin slurry during transfer; the flowability of a dry powder after exposure to high humidity

https://www.usp.org/sites/default/files/usp/document/harmonization/gen-chapter/20230428HSm99885.pdf and https://en.wikipedia.org/wiki/Flowability and https://www.sciencedirect.com/topics/materials-science/flowability

Flowability is assessed relative to a handling context and conditions (e.g., gravity discharge, pouring, conveying, pumping, geometry such as hoppers/orifices, temperature and humidity, consolidation history). In bioprocessing and pharmaceutical settings, the term is most commonly applied to powders and granular solids and evaluated using operational tests such as angle of repose, flow through an orifice, and indices derived from bulk and tapped density.

Flowability(x) → Capability(x) ∧ ∃m (MaterialEntity(m) ∧ capabilityOf(x, m))

true

capability of a material entity to move by flow

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'flowability' then x is a 'capability' that is the 'capability of' some 'material entity'

foamability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the foamability of a cell culture medium during bioreactor sparging; the foamability of a fermentation broth during agitation; the foamability of a protein formulation during pumping or filling; the foamability of a buffer containing surfactant during mixing; the foamability of a harvest fluid during transfer

https://www.sciencedirect.com/science/article/abs/pii/S0001868619303021 and https://link.springer.com/article/10.1007/s43938-023-00039-0

Foamability is realized when process conditions that promote foam formation occur, for example agitation, mixing, pumping, spraying, or gas introduction. Hence, foamability should be assessed under specified process operating conditions, because the realized amount of foam depends on both mixture composition and the process conditions.

Foamability(x) → Capability(x) ∧ ∃m∃s (MaterialEntity(m) ∧ capabilityOf(x, m) ∧ LiquidAggregateState(s) ∧ hasQuality(m, s))

true

capability of a liquid to form foam during a particular process

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'foamability' then x is a 'capability' that is the 'capability of' some 'material entity' that 'has quality' some 'liquid aggregate state'

hygroscopicity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the hygroscopicity of powdered cell culture medium during storage; the hygroscopicity of a granulated medium after exposure to humid air; the hygroscopicity of a dried excipient lot during handling; the hygroscopicity of a lyophilized drug product cake after container opening; the hygroscopicity of a salt used in buffer preparation

https://goldbook.iupac.org/terms/view/15197 and https://en.wikipedia.org/wiki/Hygroscopy

Hygroscopicity is typically realized under ambient storage or handling conditions as moisture uptake from air (commonly water vapour).

Hygroscopicity(x) → Capability(x) ∧ ∃m (MaterialEntity(m) ∧ capabilityOf(x, m))

true

capability of a material entity to attract and hold moisture from the surrounding environment

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'hygroscopicity' then x is a 'capability' that is the 'capability of' some 'material entity'

impurity fraction https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the impurity fraction of host cell protein in a purified protein solution; the impurity fraction of residual DNA in a drug substance batch; the impurity fraction of residual solvent in a dried material; the impurity fraction of an unintended product-related variant in a protein preparation; the impurity fraction of degraded protein species in a formulation; the total impurity fraction of a purified drug substance batch

http://purl.allotrope.org/ontologies/quality#AFQ_0000222

ImpurityFraction(x) → Fraction(x) ∧ ∃m(MaterialEntity(m) ∧ qualityOf(x,m) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (MaterialEntity(p) ∧ ∃r(MaterialImpurityRole(r) ∧ hasRole(p,r)))))

true

fraction of a material entity that is determined by the proportion of material considered an impurity relative to the material entity as a whole

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an ‘impurity fraction’ then x is a ‘fraction’ that is the ‘quality of’ some ‘material entity’, and if x ‘has magnitude basis in bearer part’ some p, then p is a ‘material entity’ that ‘has role’ some ‘material impurity role’

infected host cell https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ A HEK293 cell that has been infected by an adenovirus vector; MDCK cell infected by influenza virus; A CHO cell infected by vesicular stomatitis virus (VSV)

http://purl.obolibrary.org/obo/NCIT_C93037

A HEK293T cell that has been transduced with a replication-deficient AAV vector to express a therapeutic gene

InfectedHostCell(x) → Cell(x)

true

cell that is infected by a virus or another type of microorganism

There are insufficient constructs available to create a set of necessary and sufficient conditions.

if x is an 'infected host cell' then x is a 'cell'

inoculum role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the inoculum role of a thawed CHO cell suspension added to fresh medium to initiate seed expansion; the inoculum role of an E. coli starter culture added to a fermenter to initiate microbial fermentation

http://purl.obolibrary.org/obo/NCIT_C68774 and https://database.ich.org/sites/default/files/ICH_Q5A%28R2%29_Guideline_2023_1101.pdf

In this context, biological material means material that includes cells, microorganisms, viruses, infected cells, viral seed material, or other biologically derived material used to initiate or establish a biological process.

InoculumRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role held by a material entity containing biological material when it is being added, or is planned to be added, to initiate or establish biological growth, culture, infection, propagation or biological response

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'inoculum role' then x is a 'role' that is the 'role of' some 'material entity'

intact molecular mass https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the intact molecular mass of a monoclonal antibody of approximately 150 kDa; the intact molecular mass of an antibody-drug conjugate including its conjugated drug-linker species; the intact molecular mass of a glycosylated protein including its glycan forms;

intact MW

https://www.fda.gov/media/182387/download

IntactMolecularMass(x) → MolecularMass(x)

true

molecular mass of a molecular entity or molecular entity population considered in its whole, intact form, without fragmentation, cleavage, or removal of any covalently bound parts

There are insufficient constructs to define necessary and sufficient conditions.

if x is an 'intact molecular mass' then x is a 'molecular mass'

intact molecular weight

intermediate stock solution role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ intermediate stock solution role of a 0.1 M NaCl solution prepared from a 1 M stock and used to prepare a 1 mM NaCl solution for an assay

http://champ-project.org/images/ontology/cao.owl#CAO_000142

intermediate stock solution role of a 50 mM Tris-HCl buffer prepared from a 1 M stock and used directly in an assay

IntermediateStockSolutionRole(x) → StockSolutionRole(x)

true

stock solution role held by a solution when the solution is prepared by diluting another stock solution and is used, or planned to be used, to prepare further dilutions

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is an 'intermediate stock solution role' then x is a 'stock solution role'

isoelectric point https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a monoclonal antibody with pI 8.6; an enzyme with pI 5.2; a peptide with pI 9.1; an amino acid with pI 6.0; a protein variant whose pI shifts from 7.8 to 8.1 after sequence modification; a charged protein impurity with pI 4.9

http://purl.obolibrary.org/obo/NCIT_C54157

IsoelectricPoint(x) → ElectricalQuality(x) ∧ ∃m (MolecularEntity(m) ∧ qualityOf(x, m))

true

electrical quality of a molecular entity that corresponds to the pH of a homogeneous aqueous mixture at which that molecular entity has zero net electric charge and does not migrate in an electric field

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'isoelectric point' then x is an 'electrical quality' that is the 'quality of' some 'molecular entity'

manufacturing process related impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the manufacturing process related impurity role of residual Protein A ligand leached from chromatography resin into a drug substance intermediate; the manufacturing process related impurity role of host cell protein remaining in a purified monoclonal antibody intermediate; the manufacturing process related impurity role of residual host cell DNA in a drug substance intermediate; the manufacturing process related impurity role of residual solvent remaining after a synthesis or purification step;

https://www.fda.gov/media/182387/download and https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf

manufacturing process related impurity role covers impurities whose presence is attributable to the manufacturing process rather than to adventitious contamination. Planned aspects include materials, equipment, consumables, or process aids that are intentionally used in the process, such as reagents, solvents, chromatography resins, filters, tubing, bags, cleaning agents, or product-contact surfaces. Inherent aspects include materials generated or released as a normal consequence of executing the process, such as process-derived byproducts, residual intermediates, host cell proteins, residual DNA, wear particles, lubricants, extractables, or leachables. This role should be distinguished from contaminant role, which applies to material adventitiously introduced during manufacturing.

ManufacturingProcessRelatedImpurityRole(x) → MaterialImpurityRole(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m) ∧ ∃w ((MaterialProduct(w) ∨ ProcessIntermediateMaterial(w)) ∧ properContinuantPartOfAtSomeTime(m, w)))

true

material impurity role held by a material entity that is present in a process intermediate material or material product and whose presence is attributable to planned or inherent aspects of manufacturing execution

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'manufacturing process related impurity role' then x is a 'material impurity role' that is the 'role of' some 'material entity' that is a 'proper continuant part of at some time' some 'material product' or some 'process intermediate material'

mass concentration https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the mass concentration of glucose in a cell culture medium; the mass concentration of protein in a drug substance solution; the mass concentration of dissolved oxygen in culture fluid; the mass concentration of sodium chloride in a buffer solution; the mass concentration of lactate in spent culture medium

http://purl.allotrope.org/ontologies/quality#AFQ_0000167

MassConcentration(x) → Concentration(x)

true

concentration that is the mass of a specified constituent of a mixture per unit volume of that mixture

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'mass concentration' then x is a 'concentration'

master cell bank https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a master cell bank of CHO cells used to generate working cell banks for monoclonal antibody production; a master cell bank of HEK293 cells used for viral vector manufacturing; a master cell bank of a recombinant production cell line derived from a single selected clone

https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-5-d-derivation-and-characterisation-cell-substrates-used-production-biotechnologicalbiological-products-step-5_en.pdf

The master cell bank is the definitive, long-term preserved reference lot of a cell line. It serves as the primary source for the generation of working cell banks, but it may also be used directly as a production or study starting material when required. Preparation and characterization of the master cell bank must comply with ICH Q5D requirements, including full documentation of cell origin and banking procedures, and rigorous testing to confirm identity, purity (absence of microbial, viral, or other adventitious agents), and stability. Depending on the cell type and intended use, additional evaluations such as tumorigenicity or karyology are also required.

MasterCellBank(x) → CellBank(x)

true

cell bank produced in a single preparation event from a well-characterized cell line or clone, stored under validated cryogenic conditions, and established as the authoritative reference lot for direct use or the generation of further banks

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'master cell bank' then x is a 'cell bank'

material differentiation inducer https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ IL-7 and IL-15 solutions are used as differentiation inducers when added to CAR-T cell cultures to promote memory T-cell phenotype; Activin A is a differentiation inducer when added to human pluripotent stem cell cultures to direct differentiation toward definitive endoderm lineage

https://pmc.ncbi.nlm.nih.gov/articles/PMC10215625/ and https://pmc.ncbi.nlm.nih.gov/articles/PMC9043864/

MaterialDifferentiationInducer(x) ↔ MaterialFunctionalInducer(x) ∧ ∃r(MaterialDifferentiationInducerRole(r) ∧ hasRole(x, r))

material entity with a material differentiation inducer role

every instance of 'material differentiation inducer' is defined as exactly an instance of 'material functional inducer' that 'has role' some 'material differentiation inducer role'

material differentiation inducer role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ IL-7 and IL-15 solution bearing a differentiation inducer role when added to CAR-T cell cultures to promote memory T-cell phenotype; Activin A bearing a differentiation inducer role when added to human pluripotent stem cell cultures to direct differentiation toward definitive endoderm lineage

https://pmc.ncbi.nlm.nih.gov/articles/PMC10215625/ and https://pmc.ncbi.nlm.nih.gov/articles/PMC9043864/

Glucose feed added to sustain T-cell metabolism

Differentiation inducers are commonly cytokines, growth factors, or small molecules that alter developmental programs in culture

MaterialDifferentiationInducerRole(x) → MaterialFunctionalInducerRole(x)

true

role held by a material entity when it is used, or planned to be used to activate signaling pathways that drive cell fate decisions, lineage commitment, or functional specialization within a cell culture

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'material differentiation inducer role' then x is a 'material functional inducer role'

material functional inducer https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ IL-7 and IL-15 solutions are used as differentiation inducers when added to CAR-T cell cultures to promote memory T-cell phenotype; Tetracycline is a production inducer when added to a mammalian cell culture to activate a Tet-regulated promoter driving recombinant protein expression.

MaterialFunctionalInducer(x) ↔ MaterialEntity(x) ∧ ∃r(MaterialFunctionalInducerRole(r) ∧ hasRole(x, r))

material entity with a material functional inducer role

every instance of 'material functional inducer' is defined as exactly an instance of 'material entity' that 'has role' some 'material functional inducer role'

material functional inducer role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the material functional inducer role of IPTG in induction of recombinant protein expression in an E. coli lac-based expression system; the material functional inducer role of doxycycline in a tetracycline-inducible mammalian expression system; the material functional inducer role of methanol in induction of AOX1-driven expression in Komagataella phaffii; the material functional inducer role of galactose in induction of a GAL promoter system in yeast; the material functional inducer role of retinoic acid in directing cellular differentiation

MaterialFunctionalInducerRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role held by a material entity when it is used, or planned to be used, to trigger, enhance, or repress a specified cellular activity or pathway in a cell culture, organism, or microbial community beyond baseline nutrient support

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'material functional inducer role' then x is a 'role' that is the 'role of' some 'material entity'

material grade classifier https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ USP grade classification of a sodium chloride raw material lot; multi-compendial grade classification of an excipient lot; ACS reagent grade classification of a Tris buffer component; technical grade classification of a cleaning chemical;

https://alliancechemical.com/blogs/articles/chemicalgrades and https://www.biopharminternational.com/view/role-quality-standards-biomanufacturing-raw-materials and https://www.biopharminternational.com/view/case-study-pharmacopoeia-compliance-excipients-and-raw-materials-0

Material grade is a practical classification used to communicate that a material has been sourced, tested, and documented against a defined requirement set issued by a specific organization (for example, a pharmacopeia, a standards body, or a supplier). In chemical supply contexts, grades such as technical, ACS/reagent, USP/FCC/food, and water-treatment grade are used to distinguish different expectation levels for impurities, documentation, and suitability for a particular use. In biopharmaceutical manufacturing, grade distinctions are often framed operationally by what is purchased and how it is tested and governed, including compendial and multi-compendial grades (aligned to one or more monographs), and reagent grade (generally less preferred for regulated manufacture).

MaterialGradeClassifier(x) → Classifier(x) ∧ ∃m∃r (MaterialEntity(m) ∧ RequirementSpecification(r) ∧ classifies(x, m) ∧ satisfiesRequirement(m, r))

true

classifier that classifies a material entity into an organization- or authority-defined material grade based on the material entity’s conformance to a documented set of acceptance requirements and associated controls

This term is expected to remain primitive.

if x is a 'material grade classifier' then x is a 'classifier' that 'classifies' some 'material entity' that 'satisfies requirement' some 'requirement specification'

material metabolic inducer https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Lactose as a metabolic inducer in E. coli cell culture via lac operon activation; Arabinose serving as a metabolic inducer in gut microbial communities; Hydrocarbons acting as metabolic inducers in soil bacteria activating catabolic pathways

https://pmc.ncbi.nlm.nih.gov/articles/PMC3815394/

MaterialMetabolicInducer(x) ↔ MaterialFunctionalInducer(x) ∧ ∃r(MaterialMetabolicInducerRole(r) ∧ hasRole(x, r))

material entity with a material metabolic inducer role

every instance of 'material metabolic inducer' is defined as exactly an instance of 'material functional inducer' that 'has role' some 'material metabolic inducer role'

material metabolic inducer role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Lactose as a metabolic inducer in E. coli cell culture via lac operon activation; Arabinose serving as a metabolic inducer in gut microbial communities; Hydrocarbons acting as metabolic inducers in soil bacteria activating catabolic pathways

https://pmc.ncbi.nlm.nih.gov/articles/PMC3815394/

Sodium butyrate added to a HEK293 culture to boost viral vector yield

Metabolic inducers are most often substrates, substrate analogues, or related metabolites that relieve repression or otherwise activate transcription of genes for metabolic activity. They serve to adapt cellular metabolism to nutrient availability or environmental conditions, whether in controlled laboratory cultures, whole organisms, or natural microbial communities (e.g., soil, gut, biofilms).

MaterialMetabolicInducerRole(x) → MaterialFunctionalInducerRole(x)

true

role held by a material entity when it is used, or planned to be used to activate expression of enzymes or pathways involved in the utilization or regulation of metabolites within a cell culture, organism, or microbial community

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'material metabolic inducer role' then x is a 'material functional inducer role'

material production inducer https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Tetracycline is a production inducer when added to a mammalian cell culture to activate a Tet-regulated promoter driving recombinant protein expression.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8015268/pdf/nihms-1685084.pdf and https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-024-02523-w

MaterialProductionInducer(x) ↔ MaterialFunctionalInducer(x) ∧ ∃r(MaterialProductionInducerRole(r) ∧ hasRole(x, r))

material entity with a material production inducer role

every instance of 'material production inducer' is defined as exactly an instance of 'material functional inducer' that 'has role' some 'material production inducer role'

material production inducer role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Tetracycline bearing a production inducer role when added to a mammalian cell culture to activate a Tet-regulated promoter driving recombinant protein expression.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8015268/pdf/nihms-1685084.pdf and https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-024-02523-w

Glucose feed added to sustain metabolism and cell viability, which supports growth but does not trigger synthesis of a specific target product.

Production inducers are used in engineered culture systems to control when and how product formation occurs. They may be chemical compounds (e.g., tetracycline, arabinose, sodium butyrate) or environmental triggers (e.g., temperature shift, pH, light). The same compound may bear other roles in different contexts (for example, tetracycline as a therapeutic antibiotic). Environmental triggers such as temperature shifts, pH changes, oxygen limitation, or nutrient depletion can also induce product formation, but these are not material entities and do not bear a production inducer role. These will be modeled separately in a future version.

MaterialProductionInducerRole(x) → MaterialFunctionalInducerRole(x)

true

role held by a material entity when it is added, or planned to be added, to a cell culture to trigger the synthesis of a target product

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'material production inducer role' then x is a 'material functional inducer role'

miscibility https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the miscibility of ethanol and water during buffer or formulation preparation; the miscibility of a cosolvent and aqueous formulation vehicle; the miscibility of two process solvents during solvent exchange; the miscibility of oxygen and nitrogen in a gas mixture; the limited miscibility of an oil phase and aqueous phase in an emulsion-forming process; the miscibility of polymer components in a solid dispersion

https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/analytical-chemistry/purification/solvent-miscibility-table and https://goldbook.iupac.org/terms/view/MT07230

1) Miscibility concerns whether combined materials form one homogeneous phase rather than separating into multiple phases, such as liquid-liquid layering or solid-liquid phase separation. The term is used most often for liquids, but it can also be applied to gases and solid phases. 2) Whether a single phase forms and persists depends on properties of the combined materials, including chemical structure, composition, molar-mass distribution, molecular architecture, temperature, pressure, and mixing conditions.

Miscibility(x) → Capability(x) ∧ ∃m1∃m2 (MaterialEntity(m1) ∧ MaterialEntity(m2) ∧ m1 ≠ m2 ∧ capabilityOf(x, m1) ∧ capabilityOf(x, m2))

true

capability of two or more material entities to form a single homogeneous phase when combined as a mixture

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'miscibility' then x is a 'capability' that is the 'capability of' at least two distinct 'material entity'

mixed material https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a portion of air made of nitrogen, oxygen, argon, carbon dioxide, and other compositionally significant gases; a portion of phosphate-buffered saline made of water, sodium chloride, and phosphate constituents; a portion of chemically defined cell culture medium made of water, amino acids, glucose, vitamins, salts, and other constituents; a dry cell culture medium powder blend made of amino acid, sugar, salt, vitamin, and trace-element materials;

http://purl.allotrope.org/ontologies/material#AFM_0001038 and https://goldbook.iupac.org/terms/view/M03949 and http://purl.obolibrary.org/obo/CHEBI_60004

a portion of carbon dioxide gas containing trace impurities; a portion of water containing low levels of naturally occurring minerals;

1) A mixed material is made of at least two material constituents that differ in chemical identity or material composition. The constituents need not belong to different broad material categories. Two different proteins, peptides, salts, polymers, gases, or formulated materials may be distinct constituents of a mixed material. For example, a blend of two purified protein materials is a mixed material even though both constituents are proteins. 2) The constituents may be chemical substance materials or materials that are themselves mixtures. They may be distributed homogeneously or occur as distinct grains, particles, droplets, phases, or regions. In a solution, gas mixture, or alloy, the constituents may not be distinguishable at the scale of ordinary observation. In a powder blend, suspension, or emulsion, they may occur as distinguishable grains, particles, or droplets. 3) A constituent is not a minor impurity merely because it is present at a low concentration. A low-concentration constituent that is specified as part of the composition, intentionally included, or otherwise substantively contributes to the material remains a constituent. 4) Trace contaminants, incidental residual materials, degradation products, and other low-level materials may be treated as minor impurities when they do not substantively contribute to how the material is compositionally characterized. A carbon dioxide gas containing trace water or nitrogen may therefore remain a chemical substance material, whereas a specified carbon dioxide and oxygen gas blend is a mixed material. 5) A material entity is not a mixed material merely because its component parts are made of different materials. At least two distinct materials must directly constitute the material entity itself. For example, a bioreactor is not a mixed material merely because its vessel is made of stainless steel and its tubing is made of polymer. Those materials constitute different structural components rather than the bioreactor as a single material.

MixedMaterial(x) → MaterialEntity(x) ∧ ∃m∃m1(MaterialEntity(m) ∧ MaterialEntity(m1) ∧ isMadeOfAtAllTimes(x, m) ∧ isMadeOfAtAllTimes(x, m1) ∧ ¬(m = m1 ∨ isMadeOfAtAllTimes(m, m1) ∨ isMadeOfAtAllTimes(m1, m)))

true

material entity composed of at least two material constituents that are distinct in chemical identity or material composition, excluding constituents present only as minor impurities

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'mixed material', then x is a 'material entity' that 'is made of at all times' at least two material entities that are distinct and neither of which 'is made of at all times' the other

moisture content https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the moisture content of powdered cell culture medium on a wet basis; the moisture content of a lyophilized drug product cake on a dry basis; the moisture content of a resin lot after drying; the moisture content of a granulated medium before packaging; the moisture content of a dried excipient lot

http://purl.obolibrary.org/obo/NCIT_C210204

1) The defined reference mass can be the total mass of the material entity, corresponding to moisture content on a wet basis, or the dry solids mass of the material entity, corresponding to moisture content on a dry basis. 2) Although moisture content is normally interpreted as the amount of water in a material entity, some analytical methods may report a value that includes other volatile material lost during drying or measurement. For this reason, moisture content is not axiomatically restricted here to water or water molecules. Method-specific interpretations should be captured through the measurement method, result interpretation, or a more specific subclass when needed.

MoistureContent(x) → Ratio(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m))

true

ratio that is the mass of water contained in a material entity relative to a defined reference mass of that material entity

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'moisture content' then x is a 'ratio' that is the 'quality of' some 'material entity'

molar concentration https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the molar concentration of sodium chloride in a buffer solution; the molar concentration of glucose in a cell culture medium; the molar concentration of calcium ions in a media formulation;

http://purl.allotrope.org/ontologies/quality#AFQ_0000168

MolarConcentration(x) → Concentration(x)

true

concentration that is the amount of substance of a specified constituent of a mixture per unit volume of that mixture

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'molar concentration' then x is a 'concentration'

molar mass https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ The molar mass for a population of high density polyethylene polymer is 300 000 g/mol; molar mass of glucose is 180 g/mol; molar mass of sodium chloride is 58.44 g/mol

https://goldbook.iupac.org/terms/view/12214 and https://goldbook.iupac.org/terms/view/12215

1) Molar mass is mass divided by amount of substance and is expressed in units such as grams per mole or kilograms per mole. 2) When molar mass is the quality of a molecular entity, it represents the mass per mole of molecular entities of the same kind as that entity. For a non-uniform molecular entity population, it may be a specified molar-mass average, and the averaging method should be recorded with the measurement result. 3) The numerical value of a molecular mass expressed in daltons and the corresponding molar mass expressed in grams per mole are conventionally equal, but they are different quantities with different dimensions.

MolarMass(x) → Quality(x) ∧ ∃m ((MolecularEntity(m) ∨ MolecularEntityPopulation(m)) ∧ qualityOf(x, m))

true

quality that is the quality of a molecular entity or population of molecular entities, and is either the mass of one mole of that single entity, or the average mass of one mole of molecules in the population

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'molar mass' then x is a 'quality' that is the 'quality of' some 'molecular entity' or some 'molecular entity population'

molecular carrier role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ molecular carrier role of serum albumin carrying fatty acids in extracellular fluid; molecular carrier role of ferritin carrying iron atoms in its core; molecular carrier role of liposome encapsulating siRNA for cellular uptake; molecular carrier role of polyethylene glycol (PEG) acting as a carrier to improve drug solubility

https://www.labome.com/method/Cell-Culture-Media-A-Review.html and https://pub.uni-bielefeld.de/record/2943695 and https://pubmed.ncbi.nlm.nih.gov/30290072/

1) This role applies to molecular or particulate materials such as proteins, lipids, polymers, or engineered nanoparticles that transiently associate with other molecular entities to facilitate their distribution, solubility, or localization. It is distinct from logistical or container-level carriers used in supply chain contexts, which operate at the level of physical object transport. 2) Support for transport or delivery may involve binding, encapsulation, complex formation, solubilization, or other mechanisms that facilitate movement or availability of the carried molecular entity.

MolecularCarrierRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role of a material entity when it supports the transport, or delivery of one or more molecular entities in a physical, chemical, or biological system without serving primarily as a reactant in their chemical transformation

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'molecular carrier role' then x is a 'role' that is the 'role of' some 'material entity'

molecular mass https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the molecular mass of a monoclonal antibody glycoform of approximately 148 kDa; the average molecular mass of the molecules in an albumin population of approximately 66.5 kDa; the number-average molecular mass of the molecular entities in a polymer population

http://purl.allotrope.org/ontologies/quality#AFQ_0000256 and https://en.wikipedia.org/wiki/Molecular_mass

1) Molecular mass should be distinguished from molar mass. Molar mass is mass divided by amount of substance and is expressed in units such as grams per mole or kilograms per mole. 2) Molecular weight remains common in pharmaceutical, biopharmaceutical, polymer, and analytical practice. Molecular mass is the preferred term in this ontology because molecular weight is also used for the dimensionless quantity relative molecular mass

MolecularMass(x) → Mass(x) ∧ (∃m(MolecularEntity(m) ∧ qualityOf(x,m)) ∨ ∃p(MolecularEntityPopulation(p) ∧ qualityOf(x,p)))

true

mass that is either the mass of a molecular entity or an average of the masses of the molecular entities in a molecular entity population

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'molecular mass' then x is a 'mass' that is the 'quality of' some 'molecular entity' or some 'molecular entity population'

mycoplasma cell https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Mycoplasma orale detected in a mammalian cell culture; Mycoplasma hyorhinis contamination in a CHO cell culture process; Mycoplasma arginini detected during cell substrate testing; mycoplasma contamination identified in a master cell bank; mycoplasma detected in an in-process cell culture sample

https://www.sartorius.com/en/knowledge/science-snippets/what-is-mycoplasma-693938 and https://www.sciencedirect.com/science/article/abs/pii/S1045105610000783?via%3Dihub and https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.27436

Mycoplasma are wall-less bacteria with small genomes and minimal cellular architecture, which enables close association with mammalian cells and evasion of many routine microbiological detection approaches. In biopharmaceutical manufacturing, they are recognized as critical microbial contaminants of mammalian cell culture based processes. Their presence can alter cellular metabolism, affect gene expression, reduce viable cell density, and compromise product quality and safety. Because their size and lack of a rigid cell wall allow them to pass standard sterilizing filters and escape visual inspection, control strategies rely on validated multi-method detection workflows.

MycoplasmaCell(x) → BacteriumCell(x)

true

bacterium cell that lacks a rigid cell wall and is capable of infecting mammalian cells

See the primitive rationale under bacterium

if x is a 'mycoplasma cell' then x is a 'bacterium cell'

nitrogen source role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ nitrogen source role held by glutamine acting as the primary nitrogen source in CHO and hybridoma culture media; nitrogen source role held by ammonium ion serving as a nitrogen source in microbial fermentation media; role held by yeast extract serving as a complex nitrogen source in fermentation medium; role held by protein hydrolysate serving as a nitrogen-containing nutrient material in cell culture medium

https://www.sciencedirect.com/science/article/abs/pii/0168165689900096 and https://clinref.com/data/uploads/books/LehningerBiochemistry6thed.pdf

Nitrogen sources provide the assimilable nitrogen required to build cellular macromolecules and maintain metabolic activity. In mammalian-cell culture, amino acids and glutamine are typically the main nitrogen sources, supporting both biosynthesis and energy metabolism. In microbial and yeast media, nitrogen sources commonly include ammonium salts, nitrates, or urea. The type and concentration of nitrogen source influence growth kinetics, intracellular pH, energy demand, and by-product formation, making nitrogen management critical in media and feed formulation.

NitrogenSourceRole(x) → NutrientRole(x)

true

nutrient role held by a material entity that provides nitrogen for synthesis of amino acids, nucleotides, and other nitrogen-containing cellular material

if x is a 'nitrogen source role' then x is a 'nutrient role'

non-glycosylated molecular mass https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the non-glycosylated molecular mass of a monoclonal antibody heavy chain after excluding attached N-glycans; the non-glycosylated molecular mass of a glycoprotein therapeutic after enzymatic deglycosylation; the deglycosylated molecular mass of an Fc-fusion protein after removal of covalently attached glycans

https://www.fda.gov/media/182387/download

1) Non-glycosylated molecular mass characterizes a glycoprotein or population of glycoproteins by the molecular mass attributable to the non-glycan portions of the molecular entities. 2) It is commonly determined by removing covalently attached glycans through an enzymatic or chemical deglycosylation process and measuring the molecular masses of the resulting molecular entities. 3) Non-glycosylated molecular mass should be distinguished from the intact molecular mass of the glycoform population, which includes the mass contributions of covalently attached glycans.

NonGlycosylatedMolecularMass(x) → MolecularMass(x) ∧ ∃g ((Glycoprotein(g) ∨ (MolecularEntityPopulation(g) ∧ ∃p (Glycoprotein(p) ∧ hasMemberPartAtAllTimes(g, p)))) ∧ qualityOf(x, g))

true

molecular mass of a glycoprotein or population of glycoproteins that characterizes the mass contribution of its non-glycan molecular structure

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'non-glycosylated molecular mass' then x is a 'molecular mass' that is the 'quality of' some 'glycoprotein' or some 'molecular entity population' that 'has member part at all times' some 'glycoprotein'

non-glycosylated molecular weight

nutrient feed https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ concentrated glucose feed pumped to maintain glucose above a target setpoint; galactose feed added to modulate glycosylation; feed solution containing glucose, amino acids, vitamins, trace metals, and lipids added during cultivation to support high cell density and balanced metabolism

https://www.bioprocessintl.com/biochemicals-raw-materials/nutrient-supplementation-strategies-for-biopharmaceutical-production

NutrientFeed(x) ↔ MaterialEntity(x) ∧ ∃r(NutrientFeedRole(r) ∧ hasRole(x, r))

material entity with a nutrient feed role

every instance of 'nutrient feed' is defined as exactly an instance of 'material entity' that 'has role' some 'nutrient feed role'

nutrient feed role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ role held by concentrated glucose feed pumped to maintain glucose above a target setpoint; role held by a feed solution containing glucose, amino acids, vitamins, trace metals, and lipids added during cultivation to support high cell density and balanced metabolism

https://www.bioprocessintl.com/biochemicals-raw-materials/nutrient-supplementation-strategies-for-biopharmaceutical-production

role held by IPTG when it is used for induction; role held by glucose already present in the medium

This role applies to additions that are part of a controlled feeding strategy after inoculation. The purpose of nutrient feeds can include sustaining cell growth and viability, preventing nutrient depletion, extending the productive phase, optimizing productivity, or steering metabolic activity. Feeds are often chemically defined solutions and can be single or multicomponent solution containing glucose, amino acids, vitamins, trace elements, and sometimes lipids, but may also be provided as powders or slurries in some settings.

NutrientFeedRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role held by a material entity when it is added, or planned to be added, to a cell culture during cultivation or production to supply or replenish nutrients

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'nutrient feed role' then x is a 'role' that is the 'role of' some 'material entity'

nutrient role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ nutrient role borne by glucose serving as a carbon source and energy source in mammalian cell culture medium; nutrient role borne by ammonium ion serving as a nitrogen source in microbial fermentation medium; nutrient role borne by glutamine serving as a nitrogen source and energy-relevant nutrient in cell culture medium; nutrient role borne by yeast extract serving as a nutrient material in microbial culture medium; nutrient role borne by protein hydrolysate serving as a nutrient material in cell culture medium; nutrient role borne by chemically defined feed material serving as a nutrient source during fed-batch cultivation

http://purl.obolibrary.org/obo/CHEBI_33284

This role applies to material entities that are available to an organism or cell from an external material source, such as culture medium, feed material, supplement material, food material, or another surrounding material. It is intended to distinguish externally supplied nutritive material from material synthesized internally by the organism or cell. Materials bearing this role may support catabolic processes by providing energy for cellular activities, support anabolic processes by providing material used in biosynthesis, repair, maintenance, or biomass formation, or do both.

NutrientRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role held by a material entity that is made available to an organism or cell to support metabolism, growth, maintenance, or biomass formation by providing energy for cellular activities or to build or maintain cellular material

if x is a 'nutrient role' then x is a 'role' that is the 'role of' some 'material entity'

osmolality https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the osmolality of a cell culture medium after concentrated feed addition; the osmolality of a buffer solution after salt addition; the osmolality of a liquid drug product formulation adjusted using excipients; the osmolality of spent culture medium after metabolite accumulation;

http://purl.obolibrary.org/obo/PATO_0002027 and https://www.ncbi.nlm.nih.gov/sites/books/NBK567764/

Osmolality(x) → RelationalQuality(x) ∧ ∃s (Solution(s) ∧ qualityOf(x, s))

true

relational quality of a solution that is the amount of osmotically active solute entities in that solution per unit mass of solvent

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'osmolality' then x is a 'relational quality' that is the 'quality of' some 'solution'

osmolarity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the osmolarity of a cell culture medium after concentrated feed addition; the osmolarity of a buffer solution after salt addition; the osmolarity of a liquid drug product formulation adjusted using excipients;

http://purl.obolibrary.org/obo/PATO_0001655 and https://www.ncbi.nlm.nih.gov/sites/books/NBK567764/

Osmolarity is a colligative property in the sense that it depends primarily on the number of dissolved particles (osmotically active entities) rather than their chemical identity; it expresses this particle concentration on a volume-of-solution basis (i.e., osmoles of solute per liter of solution)

Osmolarity(x) → RelationalQuality(x) ∧ ∃s (Solution(s) ∧ qualityOf(x, s))

true

relational quality of a solution that is the amount of osmotically active solute entities in that solution per unit volume of that solution

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'osmolarity' then x is a 'relational quality' that is the 'quality of' some 'solution'

pH https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the pH of a phosphate-buffered saline solution measured as 7.4 at 25 °C; the pH of a chemically defined cell culture medium measured before inoculation; the pH of the aqueous phase of a mammalian cell culture during fed-batch cultivation;

http://purl.obolibrary.org/obo/PATO_0001842 and http://purl.obolibrary.org/obo/NCIT_C45997

pH is used in biopharmaceutical and laboratory practice as the standard indicator of how acidic or basic an aqueous material is. It is formally based on hydrogen-ion activity, often understood in aqueous systems through hydronium ion behavior, and is reported as a dimensionless value commonly near the 0–14 scale. In routine process and quality contexts, pH is treated as a practical measured attribute of buffers, culture media, process intermediates, and formulations. For heterogeneous materials, pH should be understood as referring to the relevant aqueous phase or sampled liquid portion, rather than to every part of the heterogeneous material.

PH(x) → RelationalQuality(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m))

true

quality of a material entity that is quantified as the negative decimal logarithm of the relative activity of hydrogen ions in that material entity

This term is expected to remain primitive

if x is 'pH' then x is a 'relational quality' that is the 'quality of' some 'material entity'

pH adjusting agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the pH adjuster role of hydrochloric acid solution during buffer preparation; the pH adjuster role of sodium hydroxide solution during formulation pH adjustment; the pH adjuster role of carbon dioxide when it is added to lower pH during a production culture process

https://www.fda.gov/media/164920/download

The role may also be assigned to materials used with hydrated, moist, or dissolvable materials, where acid-base behavior becomes relevant during hydration, dissolution, reconstitution, or processing

PHAdjustingAgentRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role of a material entity when it is used, or planned to be used to adjust pH

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'pH adjusting agent role' then x is a 'role' that is the 'role of' some 'material entity'

partial pressure https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ oxygen contributing to the total pressure of air in a bioreactor headspace; carbon dioxide contributing to the total pressure of incubator air; water vapor contributing to the total pressure of humidified air; nitrogen contributing to the total pressure of compressed air

https://goldbook.iupac.org/terms/view/P04819

PartialPressure(x) → Pressure(x) ∧ ∃m∃g(MixedMaterial(m) ∧ qualityOf(x,m) ∧ GaseousAggregateState(g) ∧ hasQuality(m,g) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (MaterialEntity(p) ∧ isMadeOfAtSomeTime(m,p))))

true

pressure that is the contribution of a particular gaseous constituent of a gas mixture to the total pressure of that mixture

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'partial pressure' then x is a 'pressure' that is the 'quality of' some 'mixed material' y that 'has quality' some 'gaseous aggregate state', and if x 'has magnitude basis in bearer part' some p, then p is a 'material entity' of which y 'is made of at some time'

pharmaceutical degradation product impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the degradation product impurity role of oxidized protein species formed during storage; the degradation product impurity role of deamidated protein variants formed under formulation pH conditions; the degradation product impurity role of hydrolyzed drug substance material formed during storage;

https://database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdf

Chemical change may be caused by light, temperature, pH, water, oxygen, process conditions, storage conditions, or reaction with an excipient or the immediate container closure system. Degradation product impurity role is used for product-related material that arises through degradation of the targeted drug substance or drug product, rather than through adventitious introduction or carryover of process materials.

PharmaceuticalDegradationProductImpurityRole(x) → PharmaceuticalProductRelatedImpurityRole(x)

true

pharmaceutical product related impurity role held by a material entity that differs from the targeted drug substance or drug product as a result of chemical change occurring during manufacture or storage

There are insufficient constructs to create necessary and sufficient conditions.

if x is a ‘pharmaceutical degradation product impurity role’ then x is a ‘pharmaceutical product related impurity role’

pharmaceutical product related impurity role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the pharmaceutical product related impurity role of high-molecular-weight monoclonal antibody aggregates in a drug substance intermediate when those aggregates increase safety risk through potential immunogenicity; the pharmaceutical product related impurity role of clipped antibody fragments in a process intermediate when the fragments reduce antigen-binding activity or Fc-mediated function; the pharmaceutical product related impurity role of oxidized monoclonal antibody species in a drug product when oxidation reduces biological activity or product stability;

https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf

PharmaceuticalProductRelatedImpurityRole(x) → MaterialImpurityRole(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m) ∧ ∃w ((MaterialProduct(w) ∨ ProcessIntermediateMaterial(w)) ∧ properContinuantPartOfAtAllTimes(m, w)))

true

material impurity role held by a material entity that is related to the targeted drug substance or drug product but is not part of the desired product composition or accepted product heterogeneity at the relevant stage and does not have properties comparable to the desired product with respect to safety, efficacy or activity

There are insufficient constructs to create necessary and sufficient conditions.

if x is a 'pharmaceutical product related impurity role' then x is a 'material impurity role' that is the 'role of' some 'material entity' that is a 'proper continuant part of at all times' some 'material product' or some 'process intermediate material'

portion of water https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ purified water; Water for Injection; process water; deionized water; drinking water; water used as a raw material in buffer preparation

1) This class represents bulk water materials whose identity is based on being composed primarily of water molecules. It is intended to capture the common practical meaning of water as used in scientific, industrial, and pharmaceutical settings, where real-world water is not expected to consist solely of H₂O molecules. 2) This class is distinct from the molecular entity water molecule, which represents H₂O at the molecular level. The molecular entity should be used when referring to individual water molecules or chemical reactions involving H₂O, whereas this class should be used for bulk water materials, water grades, and water handled in processes. 3) This class includes bulk water materials that may contain low-level dissolved gases, minerals, ions, residual disinfectants, or other minor impurities or treatment-related constituents, provided the material is still handled and classified as water. It excludes materials whose identity depends on water serving as the solvent or principal constituent of a formulated mixture, such as buffer solutions, saline solutions, culture media, cleaning solutions, or pharmaceutical formulations.

PortionOfWater(x) → ChemicalSubstanceMaterial(x) ∧ ∃m (WaterMolecule(m) ∧ isMadeOfAtAllTimes(x, m))

true

chemical substance material composed primarily of water molecules, allowing for minor impurities arising from production, handling, or environmental exchange

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is 'portion of water' then x is a 'chemical substance material' that 'is made of at all times' some 'water molecule'

portion of water for injection https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a batch of purified water classified as water for injection following manufacture and testing against the applicable water-for-injection specification; a portion of water for injection transferred from a pharmaceutical water distribution system for use in preparing a parenteral drug-product formulation; a lot of commercially supplied water classified as water for injection and documented as conforming to the applicable pharmacopeial requirements

See the expanded definition under the corresponding classifier class

PortionOfWaterForInjection(x) ↔ PortionOfWater(x) ∧ ∃y(WaterForInjectionClassifier(y) ∧ classifiedBy(x, y))

portion of water that is classified by a water for injection classifier

every instance of 'portion of water for injection' is defined as exactly an instance of 'portion of water' that is 'classified by' some 'water for injection classifier'

precipitation propensity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the precipitation propensity of a cell culture medium containing calcium and phosphate ions; the precipitation propensity of a concentrated buffer during salt addition; the precipitation propensity of a protein formulation during pH shift; the precipitation propensity of an aqueous formulation vehicle containing a poorly soluble drug substance after dilution;

PrecipitationPropensity(x) → Disposition(x) ∧ ∃m (MixedMaterial(m) ∧ dispositionOf(x, m) ∧ ∃l (LiquidAggregateState(l) ∧ hasQuality(m, l)) ∧ ∀b (hasMaterialBasisAtSomeTime(x, b) → (MaterialEntity(b) ∧ properContinuantPartOfAtSomeTime(b, m))) ∧ ∀p (hasRealization(x, p) → (Process(p) ∧ ∃o (MaterialEntity(o) ∧ hasOutput(p, o) ∧ ∃s (SolidAggregateState(s) ∧ hasQuality(o, s))))))

true

disposition of a liquid mixed material to form an insoluble solid phase from dissolved constituents

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'precipitation propensity' then x is a 'disposition' that is the 'disposition of' some 'mixed material' that 'has quality' some 'liquid aggregate state'; if x 'has material basis at some time' some b, then b is a 'material entity' that is a 'proper continuant part of at some time' that same 'mixed material'; and if x 'has realization' some p, then p is a 'process' that 'has output' some 'material entity' that 'has quality' some 'solid aggregate state'

preservation culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ transport and preservation medium cryopreservation medium

https://www.thermofisher.com/search/browse/category/us/en/90217066

Preservation culture media support transfer, holding, or storage of cells by reducing physiological stress and helping maintain viability. They may include cryoprotective agents for ultra-low temperature storage or stabilizing components for refrigerated transport. These formulations are typically sterile and liquid, and may be animal-origin-free or xeno-free. Some preservation culture media are formulated for particular cell types, such as mammalian cells or pluripotent stem cells.

PreservationCultureMedium(x) ↔ SpecializedCultureMedium(x) ∧ ∃f (CulturePreservationFunction(f) ∧ hasFunction(x, f))

specialized culture medium that has a culture preservation function

every instance of 'preservation culture medium' is defined as exactly an instance of 'specialized culture medium' when it 'has function' some 'culture preservation function'

production culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO production medium used for monoclonal antibody expression; HEK293 production medium used for viral vector production; hybridoma production medium supporting antibody secretion;

https://www.sciencedirect.com/topics/engineering/production-medium#:~:text=The%20production%20media%20have%20the,cost%20and%20to%20enhance%20yields. and https://www.fishersci.com/us/en/browse/90217078/hybridoma-myeloma-cell-culture-media

ProductionCultureMedium(x) ↔ SpecializedCultureMedium(x) ∧ ∃f (BioproductionSupportingFunction(f) ∧ hasFunction(x, f))

specialized culture medium that has a bioproduction supporting function

every instance of 'production culture medium' is defined as exactly an instance of 'specialized culture medium' when it 'has function' some 'bioproduction supporting function'

protective agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ role borne by Dimethyl sulfoxide (DMSO) added to freezing medium for cell preservation; role borne by Poloxamer 188 (Pluronic F-68) that is a surface-active nonionic polymer used in cell culture media to reduce shear stress from agitation and sparging

Covers protection from physical, mechanical, thermal, chemical, or radiative stress. Subclasses are defined by the stressor type, for example cryoprotective agent role and shear protective agent role. This notion is distinct from clinical “protective agents” used to prevent disease or treat poisoning and should not be mapped to CHEBI:50267.

ProtectiveAgentRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role of a material entity when it is used or planned to be used to protect one or more other material entities from stress or damage

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'protective agent role' then x is a 'role' that is the 'role of' some 'material entity'

protein free culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CHO protein-free media used for recombinant protein production (e.g., PF-CHO, CD-PF)

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

ProteinFreeCultureMedium(x) ↔ SerumFreeCultureMedium(x) ∧ ¬∃p (Protein(p) ∧ isMadeOfAtAllTimes(x, p))

serum free culture medium that does not include any proteins

every instance of 'protein free culture medium' is defined as exactly an instance of 'serum free culture medium' that does not 'is made of at all times' some 'protein'

protein hydrolysate https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ soy protein hydrolysate; casein hydrolysate; wheat protein hydrolysate; yeast protein hydrolysate; plant protein hydrolysate

http://id.nlm.nih.gov/mesh/D011492

ProteinHydrolysate(x) → MixedMaterial(x) ∧ ∃a (AminoAcid(a) ∧ isMadeOfAtAllTimes(x, a)) ∧ ∃p (Peptide(p) ∧ isMadeOfAtAllTimes(x, p))

true

mixed material produced by partial or extensive hydrolysis of protein-containing material and composed primarily of oligopeptides, peptides, and free amino acids

There are insufficient constructs available to create a set of necessary and sufficient conditions.

if x is a 'protein hydrolysate' then x is a 'mixed material' that 'is made of at all times' some 'amino acid' and 'is made of at all times' some 'peptide'

reconstitutability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ reconstitutability of a lyophilized drug product cake with sterile water for injection; the reconstitutability of powdered cell culture medium during media preparation; the reconstitutability of a granulated medium during liquid addition; the reconstitutability of a concentrated buffer after dilution; the reconstitutability of a dried excipient blend before formulation use; reconstitutability of concentrate orange juice with treated water

Reconstitutability(x) → Capability(x) ∧ ∃m (MaterialEntity(m) ∧ capabilityOf(x, m))

true

capability of a dried or concentrated material entity to form a liquid mixture that satisfies specified usage requirements when combined with an appropriate solvent or diluent

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'reconstitutability' then x is a 'capability' that is the 'capability of' some 'material entity'

relative abundance https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ % of high-mannose species at the end of a fed-batch step; relative abundance of a sequence variant in a drug substance lot

https://goldbook.iupac.org/terms/view/14415 and https://www.wisdomlib.org/concept/relative-abundance

1) Relative abundance is defined only after choosing a defined group of material entities as the comparison basis. The group may be small, such as the set of glycoform entities considered for one protein in one material, or very large, such as all atoms of an element in the universe. 2) The numerator may correspond to one member of the group or the combined contribution of a subset of members. The denominator is the total contribution across the entire defined group of material entities. 3) In many analytical settings, the magnitudes used in the ratio are estimated from instrument responses according to a stated method and reporting convention. 4) The defined group used for the numerator and denominator provides the comparison basis for the ratio. The quality may inhere in a broader material entity that contains the members of that group, such as a culture, mixture, intermediate pool, or product lot, with the group specifying what the relative abundance is computed over

RelativeAbundance(x) → Ratio(x)

true

ratio that is determined by the magnitude of a specified member or subset of a defined group of material entities relative to the total magnitude of that group

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'relative abundance' then x is a 'ratio'

relative humidity https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the relative humidity of incubator air at 37 °C; the relative humidity of cleanroom air during environmental monitoring; the relative humidity of humidified air supplied to a cell culture incubator; the relative humidity of air in a stability chamber; the relative humidity of air in a storage area for moisture-sensitive material

RelativeHumidity(x) → SaturationRatio(x) ∧ ∃m∃g(MixedMaterial(m) ∧ qualityOf(x,m) ∧ GaseousAggregateState(g) ∧ hasQuality(m,g))

true

saturation ratio of a gas mixture whose magnitude is the partial pressure of water vapor in that gas mixture relative to the saturation vapor pressure of water under the same temperature conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'relative humidity' then x is a 'saturation ratio' that is the 'quality of' some 'mixed material' that 'has quality' some 'gaseous aggregate state'

saturated state https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a concentrated buffer solution at the solubility limit of one buffer component during preparation; a cell culture medium at the calcium phosphate solubility limit under pH 7.0 and 37 °C conditions; a bicarbonate-buffered medium with dissolved carbon dioxide at equilibrium under 5% CO₂;

https://goldbook.iupac.org/terms/view/S05471

SaturatedState(x) → SolutionSaturationState(x)

true

material state of a solution in which the dissolved solute concentration stays at the solute's equilibrium saturation concentration in that solution under prevailing conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'saturated state' then x is a 'solution saturation state'

saturation ratio https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the dissolved oxygen saturation ratio of a cell culture medium at 37 °C; the water vapor saturation ratio of humidified incubator air at 37 °C; the carbon dioxide saturation ratio of a buffer under a 5% CO₂ gas phase;

The saturation limit is the limiting (maximum) value of the corresponding saturation-relevant quality for that material entity under those conditions (e.g., concentration relative to saturation concentration; water-vapor partial pressure relative to saturation vapor pressure).

SaturationRatio(x) → Ratio(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m))

true

ratio of a material entity whose magnitude is the magnitude of a quality of that material entity relative to the magnitude at the saturation limit for that quality under defined conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'saturation ratio' then x is a 'ratio' that is the 'quality of' some 'material entity'

serum https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ fetal bovine serum used as a cell culture supplement; bovine serum used in mammalian cell culture medium; human serum used in specialized cell culture applications; heat-inactivated serum used during cell culture;

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/serum and https://aiche.onlinelibrary.wiley.com/doi/10.1002/btpr.2706 and https://www.sigmaaldrich.com/RS/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/mammalian-cell-culture/serum-cell-tissue-faq?srsltid=AfmBOoqsTcOCHsAwgJqKH161qBbhuNQnVpAj3Pp091G9mogrrQMyek82

Serum is added to cell culture media as a complex, biologically derived supplement that supports cell viability and growth. It provides a broad spectrum of nutrients, growth factors, hormones, carrier proteins, and attachment or protective factors that collectively promote proliferation and maintain homeostasis in cultured cells. Because serum is obtained from blood and not chemically defined, its molecular composition can vary significantly between production lots and source populations.

Serum(x) → MixedMaterial(x)

true

mixed material that is obtained from blood following coagulation and removal of cells and clotting factors

This term is expected to remain primitive

if x is 'serum' then x is a 'mixed material'

serum containing culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ RPMI-1640 medium + 10% horse serum that is commonly used for hematopoietic cell lines

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

Serum-free chemically defined medium; culture medium with hydrolysates (yeastolate, soy peptone, etc.) but no animal serum

Serum-containing media are historically the most common type of complete culture media, typically supplemented with fetal bovine serum (FBS), calf serum, horse serum, or other animal sera. Serum provides a complex, undefined mix of nutrients, hormones, adhesion factors, binding proteins, protease inhibitors, and detoxifying agents, making such media broadly supportive of many cell types. However, the presence of serum introduces lot-to-lot variability and potential contaminants, including adventitious agents, endotoxin, and mycoplasma. In biomanufacturing, serum use raises regulatory concerns, and the trend has shifted toward serum-free and chemically defined media to improve reproducibility and control.

SerumContainingCultureMedium(x) ↔ CultureMedium(x) ∧ ∃y(Serum(y) ∧ hasContinuantPartAtAllTimes(x, y))

culture medium that contains serum

every instance of 'serum containing culture medium' is defined as exactly an instance of 'culture medium' that 'has continuant part at all times' some 'serum'

serum free culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ CD-CHO (chemically defined CHO medium) contains recombinant insulin and transferrin, no serum

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

CHO production medium supplemented with bovine serum albumin (BSA from serum)

Serum-free media are media formulated without serum, reducing the variability and risks associated with serum-containing formulations. They provide essential nutrients and may include recombinant proteins (e.g., insulin, transferrin), chemically defined lipids, trace elements, or other additives to support robust cell culture. Serum-free media improve reproducibility, simplify downstream purification, and are widely used in biomanufacturing because they reduce regulatory concerns and enhance lot-to-lot consistency. Many serum-free formulations are also chemically defined, but some still include hydrolysates or other complex additives.

SerumFreeCultureMedium(x) ↔ CultureMedium(x) ∧ ¬∃s (Serum(s) ∧ hasContinuantPartAtSomeTime(x, s))

culture medium that contains no serum

every instance of 'serum free culture medium' is defined as exactly an instance of 'culture medium' that does not 'has continuant part at some time' some 'serum'

shear protective agent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ shear protectant role Role held by Poloxamer 188 (Pluronic F-68) that is a surface-active nonionic polymer used in cell culture media to reduce shear stress from agitation and sparging; role borne by a Carboxymethyl cellulose (CMC) blend used to increase viscosity and protect suspended materials from shear damage

https://www.sciencedirect.com/science/article/abs/pii/S2211926422003071#:~:text=In%20addition%2C%20shear%20protectants%20are,scale%20(500%20L%20fermenter). and https://www.merckmillipore.com/deepweb/assets/sigmaaldrich/product/documents/264/391/poloxamer-optimized-tb1249en-mk.pdf

1) This role is realized through physicochemical effects that reduce mechanical or hydrodynamic stress generated by agitation, mixing, pumping, gas sparging, filling, transfer, or other handling and processing operations. Materials bearing this role may act by modifying viscosity, forming protective films, reducing damaging gas-liquid interface effects, or otherwise modulating bubble and interface dynamics. 2) The protected material is commonly present in a liquid or multiphase material such as cell culture medium, fermentation broth, formulation buffer, suspension, or process intermediate. 3) The role may be borne by a single substance or by a formulated mixture whose protective effect arises from bulk material behavior

ShearProtectiveAgentRole(x) → ProtectiveAgentRole(x)

true

protective agent role of a material entity when it is used, or planned to be used, to protect one or more other material entities from mechanical damage caused by shear stress

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'shear protective agent role' then x is a 'protective agent role'

solubility capability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ solubility capability of a powdered cell culture medium when prepared at 1X working concentration; solubility capability of a basal medium powder during media preparation; solubility capability of a granulated medium during liquid addition and mixing; solubility capability of a trace element supplement when diluted into an aqueous medium;

SolubilityCapability(x) → Capability(x) ∧ ∃m (MaterialEntity(m) ∧ capabilityOf(x, m)) ∧ ∀p (hasRealization(x, p) → (Process(p) ∧ ∃h (Solvent(h) ∧ hasInput(p, h))))

true

capability of a material entity to dissolve in a particular solvent

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'solubility capability' then x is a 'capability' that is the 'capability of' some 'material entity' and x 'has realization' only a process that 'has input' a 'solvent'

solute https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a sodium chloride portion in a buffer preparation process; a glucose portion in a culture medium preparation process; dry amino acid mixture in a feed preparation process

Solute(x) ↔ MaterialEntity(x) ∧ ∃r(SoluteRole(r) ∧ hasRole(x, r))

material entity with a solute role

every instance of 'solute' is defined as exactly an instance of 'material entity' that 'has role' some 'solute role'

solute role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a sodium chloride portion bearing a solute role in a buffer preparation process; a glucose portion bearing a solute role in a culture medium preparation process; dry amino acid mixture bearing a solute role in a feed preparation process

http://purl.allotrope.org/ontologies/role#AFRL_0000270

SoluteRole(x) → DissolutionRole(x)

true

dissolution role held by a material entity that is realized in a process where it is dissolved within another substance (the solvent) to form a solution

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'solute role', then x is a 'dissolution role'

solution https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a sodium chloride solution; a glucose feed solution; a phosphate-buffered saline solution; a protein formulation solution; an ethanol-water solution

http://purl.allotrope.org/ontologies/material#AFM_0000012

Solution(x) → MixedMaterial(x)

true

mixed material composed of one homogeneous phase in which constituent particles are not visible to the naked eye and that does not exhibit visible light scattering characteristic of a colloidal dispersion

There are insufficient constructs available to create a set of necessary and sufficient conditions.

if x is a ‘solution’, then x is a ‘mixed material’

solution saturation concentration https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ The saturation concentration of glucose in an aqueous solution at 25 °C; the saturation concentration of sodium chloride in water at 20 °C; the saturation concentration of dissolved oxygen in culture medium at 37 °C and 40% oxygen in the inlet gas; the saturation concentration of carbon dioxide in buffer at pH 7.2 under 5% CO₂ gas-phase composition; the saturation concentration of a poorly soluble drug substance in a formulation vehicle containing polysorbate at 25 °C; the saturation concentration of calcium phosphate in a cell culture medium at pH 7.0 and 37 °C; the saturation concentration of oxygen in a bioreactor culture medium at 37 °C under air sparging

https://chem.libretexts.org/Courses/Heartland_Community_College/HCC%3A_Chem_161/12%3A_Solutions/12.3%3A_Solubility_Limit_and_Saturation

Stated conditions refers to the environmental and compositional conditions under which a solubility limit is given. Examples include temperature; pressure, especially for gases; solvent identity and solvent composition; the identity and composition of any coexisting phase that constrains equilibrium, such as gas-phase partial pressures or the identity or polymorph of a solid phase; and solution-chemistry factors such as pH, ionic strength, and the presence and concentrations of other solutes or additives, including salts, cosolvents, complexing agents, or surfactants. Reported saturation concentration values are conditional on the stated condition set and may not be comparable across differing condition sets

SolutionSaturationConcentration(x) → Concentration(x) ∧ ∃s(Solution(s) ∧ qualityOf(x,s))

true

concentration of a dissolved solute in a solution at the solubility limit of that solute under stated conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'solution saturation concentration' then x is a 'concentration' that is the 'quality of' some 'solution'

solution saturation ratio https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the solution saturation ratio of dissolved oxygen in cell culture medium at 37 °C during bioreactor operation; the solution saturation ratio of carbon dioxide in a bicarbonate-buffered medium under 5% CO₂;

https://goldbook.iupac.org/terms/view/S05476

SolutionSaturationRatio(x) → SaturationRatio(x) ∧ ∃s(Solution(s) ∧ qualityOf(x,s))

true

saturation ratio of a solution whose magnitude is the concentration of a dissolved solute in that solution relative to the saturation concentration of that solute for the solution under the same conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'solution saturation ratio' then x is a 'saturation ratio' that is the 'quality of' some 'solution'

solution saturation state https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a poorly soluble drug substance remaining dissolved above its equilibrium saturation concentration after solvent shift into an aqueous formulation vehicle; a formulation component remaining dissolved temporarily after cooling from room temperature to refrigerated storage; a sodium chloride buffer in which additional sodium chloride can still dissolve at 20 °C; a cell culture medium in which calcium and phosphate remain below the precipitation limit at pH 7.0 and 37 °C; a cell culture medium at the calcium phosphate solubility limit under pH 7.0 and 37 °C conditions; a bicarbonate-buffered medium with dissolved carbon dioxide at equilibrium under 5% CO₂;

https://goldbook.iupac.org/terms/view/12730

Prevailing conditions in this context are the environmental and compositional variables that determine the solute’s equilibrium solubility for that solution at that time, typically including temperature and pH, and, where relevant, solvent composition (e.g., cosolvents), ionic strength, and the presence of other solutes/excipients that measurably shift solubility.

SolutionSaturationState(x) → MaterialState(x) ∧ ∃s (Solution(s) ∧ isMaterialStateOf(x, s))

true

material state of a solution in which the dissolved solute concentration stays below, at, or above the solute's equilibrium saturation concentration in that solution under prevailing conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'solution saturation state' then x is a 'material state' that 'is material state of' some 'solution'

solvent https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a purified water portion in a buffer preparation process; a water for injection portion in a formulation preparation process;

Solvent(x) ↔ MaterialEntity(x) ∧ ∃r(SolventRole(r) ∧ hasRole(x, r))

material entity with a solvent role

every instance of 'solvent' is defined as exactly an instance of 'material entity' that 'has role' some 'solvent role'

solvent role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a purified water portion bearing a solvent role in a buffer preparation process; a water for injection portion bearing a solvent role in a formulation preparation process;

http://purl.allotrope.org/ontologies/role#AFRL_0000269

The bearer of solvent role may be a pure substance or a mixture (e.g., a buffer or culture medium)

SolventRole(x) → DissolutionRole(x)

true

dissolution role held by a material entity that is realized in a process where it dissolves another substance (the solute) to form a solution

There are insufficient constructs to define necessary and sufficient conditions.

if x is a 'solvent role' then x is a 'dissolution role'

specialized culture medium https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Human-Mesenchymal-XF-Expansion-Medium; Hybridoma Myeloma Cell Culture Media

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

Specialized media are culture media developed from basal or chemically defined formulations and optimized for specific biological contexts. They may contain tailored supplements such as growth factors, cytokines, or differentiation-inducing agents, and are used either to maintain a desired cell phenotype (e.g., pluripotent stem cells) or to drive a specific outcome (e.g., neuronal differentiation, hybridoma antibody secretion). Specialized media are frequently supplied as ready-to-use commercial products and may be serum-containing or chemically defined depending on the application. They are important tools in both research and biomanufacturing, where controlled and reproducible conditions are required for specialized processes.

SpecializedCultureMedium(x) ↔ CultureMedium(x) ∧ ∃f (SpecializedCultureMediumFunction(f) ∧ hasFunction(x, f))

culture medium that has a specialized culture medium function

every instance of 'specialized culture medium' is defined as exactly an instance of 'culture medium' when it 'has function' some 'specialized culture medium function'

specialized culture medium function https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the cell proliferation supporting function borne by a T-cell expansion medium containing IL-7 and IL-15; the bioproduction supporting function borne by a CHO production medium used during monoclonal-antibody expression; the specialized culture medium function borne by a medium formulated for expansion of human mesenchymal cells

https://www.labome.com/method/Cell-Culture-Media-A-Review.html

SpecializedCultureMediumFunction(x) → DesignedFunction(x) ∧ ∃m (CultureMedium(m) ∧ inheresIn(x, m)) ∧ ∃r (RequirementSpecification(r) ∧ satisfiesRequirement(x, r))

true

designed function that inheres in a culture medium and is specified to satisfy the culture requirements of a particular cell type, tissue, microorganism, or cultivation application, often through selective supplements or tailored nutrient formulations

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'specialized culture medium function' then x is a 'designed function' that 'inheres in' some 'culture medium' and 'satisfies requirement' some 'requirement specification'

spent culture medium state https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ State of culture medium in a CHO fed-batch culture after several days of glucose and amino acid consumption; State of culture medium containing accumulated lactate and ammonia during mammalian cell cultivation; State of culture medium containing secreted recombinant protein and host cell proteins at harvest; State of culture medium after feed addition and cellular metabolism have changed its nutrient and metabolite profile; State of culture medium sampled from a bioreactor during cultivation for extracellular metabolite analysis; State of culture medium remaining after cultivation before clarification or downstream processing

A spent culture medium state is a state of culture medium during or after cultivation. It may involve depletion of nutrients, accumulation of metabolites such as lactate or ammonia, secretion of product or host cell proteins, changes in pH or osmolality, or other extracellular compositional changes. The term does not imply that the medium is fully exhausted or unsuitable for continued cultivation.

SpentCultureMediumState(x) → MaterialState(x) ∧ ∃m (CultureMedium(m) ∧ isMaterialStateOf(x, m))

true

material state of culture medium that has participated in a cell cultivation process and is characterized by compositional changes caused by cellular activity, process additions, or accumulation of extracellular material

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'spent culture medium state' then x is a 'material state' that 'is material state of' some 'culture medium'

stock solution role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the stock solution role of a 1 M glucose solution used to prepare lower-concentration glucose additions for cell culture medium; the stock solution role of a 100 mM IPTG solution used to prepare induction solutions; the stock solution role of a concentrated sodium hydroxide solution used for preparation of pH adjustment solutions;

https://goldbook.iupac.org/terms/view/09050 and https://www.sciencedirect.com/topics/mathematics/stock-solution

1) A stock solution is usually prepared at a higher concentration than is needed for its later use and is diluted to obtain the required concentration before use. 2) Because the solute concentration is accurately known, stock solutions support reproducible preparation of other solutions, mixtures, assay materials, formulation materials, culture media, or process materials. Measured portions may be diluted or added as components in planned processes. Their reliability depends on correct preparation and appropriate storage conditions, since degradation, precipitation, contamination, or evaporation can introduce concentration errors over time. 3) Dilution of a stock solution may produce a working solution or an intermediate stock solution

StockSolutionRole(x) → Role(x) ∧ ∃s (Solution(s) ∧ roleOf(x, s))

true

role held by a solution that is prepared with an accurately known solute concentration so that measured portions can be diluted to the concentration needed for a particular use

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'stock solution role' then x is a 'role' that is the 'role of' some 'solution'

supersaturated state https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a poorly soluble drug substance remaining dissolved above its equilibrium saturation concentration after solvent shift into an aqueous formulation vehicle; a formulation component remaining dissolved temporarily after cooling from room temperature to refrigerated storage; a concentrated buffer component remaining dissolved above its equilibrium solubility before precipitation begins;

https://goldbook.iupac.org/terms/view/12730

SupersaturatedState(x) → SolutionSaturationState(x)

true

solution saturation state in which the dissolved solute concentration stays above the solute's equilibrium saturation concentration in that solution under prevailing conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'supersaturated state' then x is a 'solution saturation state'

surface tension https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the surface tension of a protein formulation containing polysorbate; the surface tension of a liquid drug product during fill-finish; the surface tension of a buffer solution used for membrane wetting; the surface tension of a cleaning solution used for equipment cleaning; the surface tension of a cell culture medium containing antifoam or surfactant;

http://purl.obolibrary.org/obo/PATO_0001461 and https://goldbook.iupac.org/terms/view/S06192

SurfaceTension(x) → Quality(x) ∧ ∃m∃s (MaterialEntity(m) ∧ qualityOf(x, m) ∧ LiquidAggregateState(s) ∧ hasQuality(m, s))

true

quality of a liquid material entity that is the resistance of the liquid surface to an increase in surface area, arising from unbalanced cohesive forces between molecules at the liquid surface

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'surface tension' then x is a 'quality' that is the 'quality of' some 'material entity' that 'has quality' some 'liquid aggregate state'

surfactant https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ polysorbate 80 when added to culture medium to improve wetting and dispersion; Sodium dodecyl sulfate (SDS) when added to aqueous buffer to reduce interfacial tension

http://purl.obolibrary.org/obo/CHEBI_35195

Surfactant(x) ↔ MaterialEntity(x) ∧ ∃r(SurfactantRole(r) ∧ hasRole(x,r))

material entity with a surfactant role

every instance of 'surfactant' is defined as exactly an instance of 'material entity' that 'has role' some 'surfactant role'

surfactant role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ Role borne by polysorbate 80 when added to culture medium to improve wetting and dispersion; Role borne by Sodium dodecyl sulfate when added to aqueous buffer to reduce interfacial tension

http://purl.obolibrary.org/obo/CHEBI_35195

The term medium refers broadly to a surrounding phase system, such as a liquid, gas, or solid, not only to culture medium. Materials bearing a surfactant role are used to promote wetting, dispersion, emulsification, foam control, or cleaning by reducing surface or interfacial tension. A material bearing this role may be a single compound or a formulated mixture.

SurfactantRole(x) → Role(x) ∧ ∃m (MaterialEntity(m) ∧ roleOf(x, m))

true

role of a material entity when it is used, or planned to be used, to lower the surface tension of a medium or the interfacial tension between phases by preferentially adsorbing at liquid-vapor or other phase interfaces

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'surfactant role' then x is a 'role' that is the 'role of' some 'material entity'

tapped density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the tapped density of powdered cell culture medium measured during raw material characterization; the tapped density of a specific grade of granular PVC resin measured with a tap density tester to characterize a product lot; the tapped density of an excipient powder used in tablet formulation development;

https://www.3p-instruments.com/measurement-methods/density-tapping-volumetry/

TappedDensity(x) → MassDensity(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m) ∧ ∃f (ParticulateForm(f) ∧ hasQuality(m, f)))

true

mass density of a particulate material that is the mass per tapped volume occupied by the material after tapping until little or no further volume change is observed

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a 'tapped density' then x is a 'mass density' that is the 'quality of' some 'material entity' that 'has quality' some 'particulate form'

tap density

total cell count https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the total cell count of a seed bioreactor culture sample measured by an automated cell counter using trypan blue exclusion; the total cell count of a production bioreactor culture sample reported by an automated cell counter as the combined count of viable and non-viable cells;

http://purl.allotrope.org/ontologies/quality#AFQ_0000186

Total cell count includes both viable and non-viable cells in the assessed cell population. A count restricted to viable cells is represented separately as viable cell count.

TotalCellCount(x) → CellCount(x)

true

cell count that is the number of all cells present as parts of a material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'total cell count' then x is a 'cell count'

total cell density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the total cell density of a bioreactor culture sample measured by an automated cell counter; the total cell density of a CHO cell culture during production; the total cell density of a seed train culture before inoculation;

https://www.sciencedirect.com/topics/medicine-and-dentistry/cell-density and https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/photometry-and-reflectometry/cell-density-measurement-by-od600-method?srsltid=AfmBOoqxMLTlROXCkIoHCGlcNFWUSSZvftakFCMkyCL5l9gpB-s7B3yL and http://purl.allotrope.org/ontologies/quality#AFQ_0000181

Total cell density accounts for both viable and non-viable cells in the assessed cell population. A cell density restricted to viable cells is represented as viable cell density.

TotalCellDensity(x) → CellDensity(x)

true

cell density that is the total number of cells per unit size

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a ‘total cell density’ then x is a ‘cell density’

unsaturated state https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a sodium chloride buffer in which additional sodium chloride can still dissolve at 20 °C; a cell culture medium in which calcium and phosphate remain below the precipitation limit at pH 7.0 and 37 °C; a formulation vehicle containing a poorly soluble drug substance below its equilibrium saturation concentration at 25 °C;

https://goldbook.iupac.org/terms/view/15369

UnsaturatedState(x) → SolutionSaturationState(x)

true

material state of a solution in which the dissolved solute concentration stays below the solute's equilibrium saturation concentration in that solution under prevailing conditions

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is an 'unsaturated state' then x is a 'solution saturation state'

viability status https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the viability of a CHO cell classified as viable in a FACS assay using propidium iodide exclusion; the viability of a T cell classified as viable in a FACS assay using 7-AAD exclusion;

http://purl.obolibrary.org/obo/PATO_0000169

Viability status is used as the individual-level parent quality for qualitative states such as viable and dead. It should be distinguished from viability ratio, which is a population-level ratio determined by the number of viable members relative to the total number of relevant members.

ViabilityStatus(x) → Quality(x) ∧ ∃m (MaterialEntity(m) ∧ qualityOf(x, m))

true

quality of a biological material entity by virtue of whether that entity is alive and capable of maintaining or recovering relevant physiological activity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'viability status' then x is a 'quality' that is the 'quality of' some 'material entity'

viable https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ a CHO cell classified as viable after trypan blue exclusion; a T cell classified as viable in a FACS assay using 7-AAD exclusion; a microbial cell capable of forming a colony after plating

http://purl.obolibrary.org/obo/PATO_0000719

Viable(x) → ViabilityStatus(x)

true

viability status of a biological material entity that is alive and capable of maintaining or recovering relevant physiological activity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is 'viable' then x is a 'viability status'

viable cell count https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the viable cell count of a thawed cell suspension after viability staining; the viable cell count of a seed culture before passaging;

http://purl.allotrope.org/ontologies/quality#AFQ_0000185

ViableCellCount(x) → CellCount(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (Cell(p) ∧ ∃v(Viable(v) ∧ hasQuality(p,v))))

true

cell count that is the number of viable cells that are present as parts of a material entity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'viable cell count' then x is a 'cell count', and if x 'has magnitude basis in bearer part' some p, then p is a 'cell' that 'has quality' some 'viable'

viable cell density https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the viable cell density of a CHO cell culture during production; the viable cell density of a bioreactor culture sample measured by an automated cell counter; the viable cell density of a seed train culture before inoculation;

VCD

https://www.sartorius.com/download/501934/online-monitoring-of-viable-cell-concentrations-in-small-bioreactors-data.pdf and http://purl.allotrope.org/ontologies/quality#AFQ_0000182

Viable cell density accounts only for cells that are alive and capable of maintaining essential physiological activities such as metabolism, growth, and proliferation. It is commonly reported as viable cells per unit volume, such as cells/mL, or viable cells per unit area, such as cells/cm².

ViableCellDensity(x) → CellDensity(x) ∧ ∀p(hasMagnitudeBasisInBearerPart(x,p) → (Cell(p) ∧ ∃d(Viable(d) ∧ hasQuality(p,d))))

true

cell density that is the number of viable cells per unit size

There are insufficient constructs for creating a set of necessary and sufficient conditions.

if x is a 'viable cell density' then x is a 'cell density', and if x 'has magnitude basis in bearer part' some p, then p is a 'cell' that 'has quality' some 'viable'

viable cell population https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the subpopulation of CHO cells within a mixed cell culture that is capable of continued growth and proliferation under suitable culture conditions, as determined by a validated cell viability assay; the population of colony-forming cells identified in a clonogenic assay following exposure of a broader cell population to a process stress; the population of cells recovered from a cryopreserved cell bank vial that retains the capacity to resume proliferation after thawing and transfer to suitable culture medium;

ViableCellPopulation(x) ↔ CellPopulation(x) ∧ ∃y(Cell(y) ∧ ∃q(Viable(q) ∧ hasQuality(y, q)) ∧ hasMemberPartAtSomeTime(x, y)) ∧ ∀z(hasMemberPartAtSomeTime(x, z) → (Cell(z) ∧ ∃r(Viable(r) ∧ hasQuality(z, r))))

cell population consisting of only viable cells

every instance of 'viable cell population' is defined as exactly an instance of 'cell population' that 'has member part at some time' some 'cell' that 'has quality' some 'viable' and 'has member part at some time' only 'cell' that 'has quality' some 'viable'

virus https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ reovirus that contaminates a cell culture process; adenovirus used as a viral vector; lentiviral vector produced in a manufacturing process;

http://id.nlm.nih.gov/mesh/D014780

Virus(x) → Object(x)

true

minute infectious agent that has a DNA or RNA genome, lacks independent metabolism, and replicates only through use of a living host cell

This term is expected to remain primitive, detailed treatment of a virus should be utilized if needed from a biological ontology

if x is a 'virus' then x is an 'object'

virus seed https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ master virus seed stock for production of an adenovirus-based vaccine, consisting of multiple frozen portions derived from a single characterized virus preparation; working virus seed vials prepared from the master virus seed and used to initiate manufacturing of viral vectors for gene therapy production

https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q5ar2-guideline-viral-safety-evaluation-biotechnology-products-derived-cell-lines-human-or-animal-origin-step-5_en.pdf and https://extranet.who.int/prequal/glossary-acronyms/s#:~:text=A%20master%20seed%20lot%20

VirusSeed(x) → ObjectAggregate(x)

true

object aggregate consisting of containers whose contents are portions of a virus preparation derived from a single defined virus source and maintained as a referenceable lot

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'virus seed' then x is an 'object aggregate'

water for injection classifier https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ USP Water for Injection classification of a pharmaceutical water lot; Ph. Eur. Water for Injection classification of water used in sterile drug product manufacturing; WFI classification of water supplied from a qualified pharmaceutical water system; WFI classification of water used for final formulation of an injectable drug product;

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/water-pharmaceutical-use and https://www.ema.europa.eu/en/documents/scientific-guideline/note-guidance-quality-water-pharmaceutical-use_en.pdf and https://www.cytivalifesciences.com/en/us/insights/what-is-water-for-injection

1) The Water for Injection (WFI) grade is a compendial classification applied to water when conformance to an applicable WFI monograph has been demonstrated. In the European context, EMA guidance points to compliance with the European Pharmacopoeia WFI monograph. In the U.S. context, FDA inspection guidance frames WFI as a USP monograph-defined water grade. 2) In regulatory and GMP practice, WFI is best treated as a compendial-grade designation: a batch or portion of water is WFI because it meets the applicable WFI monograph requirements, and it can lose that designation if storage or distribution conditions allow microbial proliferation, endotoxin risk, or other quality risks to rise. 3) The classifier is constrained to classify water and to indicate that purity is a relevant reported quality for the classified water;

WaterForInjectionClassifier(x) → CompendialGradeClassifier(x) ∧ ∃w (PortionOfWater(w) ∧ classifies(x, w) ∧ ∃p (Purity(p) ∧ hasQuality(w, p)))

true

compendial grade classifier that classifies a portion of water that conforms to the requirements stated in a Water for Injection pharmacopeial monograph and thus has very high purity

There are insufficient constructs for creating a set of necessary and sufficient conditions

if x is a 'water for injection classifier' then x is a 'compendial grade classifier' that 'classifies' some 'portion of water' that 'has quality' some 'purity'

wettability https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ the wettability of powdered cell culture medium during reconstitution; the wettability of granular medium during liquid addition; the wettability of a filter membrane during pre-wetting; the wettability of chromatography resin beads during slurry preparation;

1) Being wetted means a liquid spreads over a solid material and maintains contact with it at the solid–liquid interface, rather than beading up into discrete droplets, under the prevailing interfacial conditions. 2)Wettability is realized in liquid–solid contact situations and is influenced by interfacial interactions between the solid and the liquid and by the surrounding phase. The same concept applies to a continuous solid surface and to particulate or granular solids, where the capability is manifested through wetting of the available solid surfaces and, at the bulk level, through penetration of liquid into the material and reduction of persistent dry regions. In practice, contact angles are a common way to operationalize wettability for smooth surfaces, while powders are often characterized through liquid uptake, immersion, or penetration behaviors.

https://www.sciencedirect.com/topics/materials-science/wettability and https://store.astm.org/d7334-08.html and https://www.iso.org/obp/ui#iso:std:iso:862:ed-1:v1:en:term:99 and https://onlinelibrary.wiley.com/doi/abs/10.1002/ppsc.200400931

Wettability(x) → Capability(x) ∧ ∃m∃s (MaterialEntity(m) ∧ capabilityOf(x, m) ∧ SolidAggregateState(s) ∧ hasQuality(m, s)) ∧ ∀p (hasRealization(x, p) → (Process(p) ∧ ∃l∃ls (MaterialEntity(l) ∧ LiquidAggregateState(ls) ∧ hasQuality(l, ls) ∧ hasParticipantAtSomeTime(p, l))))

true

capability of a solid material to be wetted by a liquid

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'wettability' then x is a 'capability' that is the 'capability of' some 'material entity' that 'has quality' some 'solid aggregate state', and if x 'has realization' some p, then p is a 'process' that 'has participant at some time' some 'material entity' that 'has quality' some 'liquid aggregate state'

working cell bank https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ working cell bank of CHO cells used to inoculate production seed trains; a working cell bank generated from a master cell bank for monoclonal antibody manufacturing; a working cell bank of HEK293 cells used for viral vector production;

https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-5-d-derivation-and-characterisation-cell-substrates-used-production-biotechnologicalbiological-products-step-5_en.pdf

The source cells are expanded into a homogeneous suspension from one or more vials of the master cell bank, dispensed into multiple uniform containers, and cryopreserved under validated long-term storage conditions. The resulting working cell bank serves as the routine production cell source, allowing repeated use while minimizing the need to access the master cell bank directly.

WorkingCellBank(x) → CellBank(x)

true

cell bank prepared from cells recovered from one or more containers of a master cell bank and stored under validated cryogenic conditions as a source of cryopreserved cells for routine use in research, development, or manufacturing

There are insufficient constructs to create a set of necessary and sufficient conditions.

if x is a 'working cell bank' then x is a 'cell bank'

working solution role https://spec.industrialontologies.org/ontology/biopharma/BiopharmaMaterial/ 50 mM Tris-HCl prepared by diluting a 1 M Tris stock solution for use in an enzymatic assay

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/m10-bioanalytical-method-validation-and-study-sample-analysis and http://champ-project.org/images/ontology/cao.owl#CAO_000214

A 1 M Tris-HCl stock solution stored for later dilutions

Working solutions are derived from stock solutions and adjusted to the concentrations required for assays, buffer systems, culture additives, or other procedures. They are intended for immediate or short-term use and are usually less concentrated than the stock from which they are prepared.

WorkingSolutionRole(x) → Role(x) ∧ ∃s (Solution(s) ∧ roleOf(x, s))

true

role held by a solution when the solution is prepared from a stock solution or intermediate stock solution at the concentration required for use in a planned process that is not itself a dilution process

There are insufficient constructs to create a set of necessary and sufficient conditions

if x is a 'working solution role' then x is a 'role' that is the 'role of' some 'solution'