cell bleed process

IRI: https://spec.industrialontologies.org/ontology/construct/CellBleedProcess

Defined In: https://spec.industrialontologies.org/ontology/biopharma/BiopharmaManufacturingExecution/

SubClass Of: material removal process

Class Hierarchy

owl:Thing › bfo:entity › bfo:occurrent › bfo:process › planned process › material removal process › cell bleed process

Definition

material removal process in which a portion of cell-containing culture material is withdrawn from a cell culture during an ongoing culture process to regulate culture properties such as viable cell density, biomass concentration, or metabolite accumulation

Explanatory Notes

A cell bleed process is commonly used in perfusion culture processes to regulate viable cell density or biomass concentration, but it is not limited to continuous process operating mode. It may also occur in semi-continuous or other ongoing culture processes when cell-containing culture material is deliberately withdrawn to regulate culture properties. It should be distinguished from terminal harvest, which removes culture material to collect product or conclude the culture process, and from sampling, which removes material for measurement or testing

Examples

• In a perfusion culture of CHO cells producing a monoclonal antibody, a controlled daily bleed of 10% of the reactor volume is performed to maintain cell density within the target range (e.g., 20–30 × 10⁶ cells/mL). This prevents overgrowth, stabilizes residence time distribution, and avoids excessive accumulation of lactate and ammonia that could impair productivity or product quality.

Counter-Examples

• At the end of a fed-batch run, the entire bioreactor contents are removed to recover product (harvesting). Although this involves material removal, it is not considered bleeding because the goal is not to regulate culture properties during an ongoing process, but rather to terminate the culture and collect the final product.

Adapted From

• https://documents.thermofisher.com/TFS-Assets/BPD/Reference-Materials/perfusion-terminology-white-paper.pdf

Primitive Class

This class is declared primitive and it does not have necessary and sufficient condiftions defined.

Primitive Rationale

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

Formal Axioms

First-Order Logic Axioms

CellBleedProcess(x) → MaterialRemovalProcess(x) ∧ ∃c ∃sr ∃o ∃tr ∃p (CellCulture(c) ∧ hasParticipantAtSomeTime(x, c) ∧ MaterialWithdrawalSourceRole(sr) ∧ hasRole(c, sr) ∧ MaterialEntity(o) ∧ hasSpecifiedOutput(x, o) ∧ ∃cp (CellPopulation(cp) ∧ hasContinuantPartAtAllTimes(o, cp)) ∧ TransferredMaterialRole(tr) ∧ hasRole(o, tr) ∧ PlannedProcess(p) ∧ occursDuring(x, p) ∧ hasParticipantAtSomeTime(p, c))

Semi-Formal Natural Language Axioms

if x is a ‘cell bleed process’ then x is a ‘material removal process’ that ‘has participant at some time’ some ‘cell culture’ that ‘has role’ some ‘material withdrawal source role’, ‘has specified output’ some ‘material entity’ that ‘has continuant part at all times’ some ‘cell population’ and ‘has role’ some ‘transferred material role’, and ‘occurs during’ some ‘planned process’ that ‘has participant at some time’ that same ‘cell culture’

Description Logic

constr:CellBleedProcess ⊑ constr:MaterialRemovalProcess

constr:CellBleedProcess ⊑ ∃ bfo:has_participant_at_some_time .(constr:CellCulture ⊓ ∃ constr:hasRole .constr:MaterialWithdrawalSourceRole)

constr:CellBleedProcess ⊑ ∃ constr:hasSpecifiedOutput .(bfo:material_entity ⊓ ∃ bfo:has_continuant_part_at_all_times .constr:CellPopulation ⊓ ∃ constr:hasRole .constr:TransferredMaterialRole)

constr:CellBleedProcess ⊑ ∃ constr:occursDuring .(constr:PlannedProcess ⊓ ∃ bfo:has_participant_at_some_time .constr:CellCulture)

SubClassOf: constr:MaterialRemovalProcess

SubClassOf: bfo:has_participant_at_some_time some (constr:CellCulture and constr:hasRole some constr:MaterialWithdrawalSourceRole)

SubClassOf: constr:hasSpecifiedOutput some (bfo:material_entity and bfo:has_continuant_part_at_all_times some constr:CellPopulation and constr:hasRole some constr:TransferredMaterialRole)

SubClassOf: constr:occursDuring some (constr:PlannedProcess and bfo:has_participant_at_some_time some constr:CellCulture)