seed train
IRI: https://spec.industrialontologies.org/ontology/construct/SeedTrain
Defined In: https://spec.industrialontologies.org/ontology/biopharma/BiopharmaManufacturingExecution/
SubClass Of: manufacturing process
Class Hierarchy
owl:Thing › bfo:entity › bfo:occurrent › bfo:process › planned process › manufacturing process › seed train
Definition
manufacturing process composed of a sequence of cell culture expansion processes occurring at increasing scales and that has as its specified output a cell culture at the required density to inoculate a production culture process
Semi-Formal Definition:
every instance of ‘seed train’ is defined as exactly an instance of ‘manufacturing process’ that ‘has input’ some ‘cell culture’, ‘has occurrent part’ some ‘cell culture expansion process’, and ‘has specified output’ some ‘cell culture’ that ‘satisfies requirement’ some ‘input specification’ that is ‘continuant part of at all times’ some ‘plan specification’ that ‘prescribes’ some ‘production culture process’
Explanatory Notes
1) The seed train is a series of steps used to generate the sufficient amount of viable cells for large-scale production of vaccines, viral vectors, monoclonal antibodies and other biologics. The purpose of the seed train is to progressively grow and expand the initial small-scale cell culture to inoculate the large-scale bioreactor for higher capacity production. 2) A single cell culture expansion process within the seed train is also called a “passage” 3) The following terms are commonly used when discussing a seed train or inoculum expansion with multiple steps: “N” refers to the production vessel; “N-1” refers to the final expansion used to inoculate the production vessel; “N-2” refers to the expansion before that, used to inoculate the N-1, and so on
Examples
- a monoclonal antibody seed train expanded CHO cells through sequential steps in shake flasks, a 10 L bioreactor, and a 200 L seed bioreactor based on target inoculation density; a seed train progressing through shake flasks and seed bioreactors to generate inoculum for a 5,000 L production bioreactor
Adapted From
- https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-q12-technical-and-regulatory-considerations-pharmaceutical-product-lifecycle-management-step-2b-annexes-first-version_en.pdf and https://20669391.fs1.hubspotusercontent-na1.net/hubfs/20669391/social-uploaded-images/SUIS/MK_WP13194EN%20Regulatory%20Perspectives%20Implementing%20Seed%20Train%20Intensification%20using%20HCDC%20-%20MK.pdf
Formal Axioms
First-Order Logic Definition
SeedTrain(x) ↔ ManufacturingProcess(x) ∧ ∃a (CellCulture(a) ∧ hasInput(x, a)) ∧ ∃b (CellCultureExpansionProcess(b) ∧ hasOccurrentPart(x, b)) ∧ ∃c (CellCulture(c) ∧ hasSpecifiedOutput(x, c) ∧ ∃i ∃p ∃y (InputSpecification(i) ∧ PlanSpecification(p) ∧ satisfiesRequirement(c, i) ∧ continuantPartOfAtAllTimes(i, p) ∧ ProductionCultureProcess(y) ∧ prescribes(p, y)))
Description Logic
constr:SeedTrain ≡ constr:ManufacturingProcess ⊓ ∃ bfo:has_occurrent_part .constr:CellCultureExpansionProcess ⊓ ∃ constr:hasInput .constr:CellCulture ⊓ ∃ constr:hasSpecifiedOutput .(constr:CellCulture ⊓ ∃ constr:satisfiesRequirement .(constr:InputSpecification ⊓ ∃ bfo:continuant_part_of_at_all_times .(constr:PlanSpecification ⊓ ∃ constr:prescribes .constr:ProductionCultureProcess)))
constr:SeedTrain ⊑ constr:ManufacturingProcess
constr:SeedTrain ⊓ constr:BiomanufacturingProductionProcess ⊑ ⊥
EquivalentTo: constr:ManufacturingProcess and bfo:has_occurrent_part some constr:CellCultureExpansionProcess and constr:hasInput some constr:CellCulture and constr:hasSpecifiedOutput some (constr:CellCulture and constr:satisfiesRequirement some (constr:InputSpecification and bfo:continuant_part_of_at_all_times some (constr:PlanSpecification and constr:prescribes some constr:ProductionCultureProcess)))
SubClassOf: constr:ManufacturingProcess
constr:SeedTrain DisjointWith: constr:BiomanufacturingProductionProcess