]> Monitoring And Control Ontology This module contains terms and relations necessary for representing the planning and execution of monitoring and/or controlling for both laboratory and manufacturing scale. 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 Monitoring And Control Ontology

control strategy control plan specification integrated control strategy A control strategy for sterile filling includes gravimetric sensors to monitor and regulate fill volume (process parameter), cleanroom environmental monitoring to monitor particulate levels and temperature (quality attributes), and automated rejection of out-of-spec units. The process performance indicator is fill volume deviation rate, calculated as the percentage of vials outside volume targets; A control strategy for fed-batch cell culture includes specifying a gas controller to regulate dissolved oxygen (process parameter), a pH control loop to maintain pH within range (process parameter), and monitoring of cell viability over time as a process performance indicator. It also specifies that the glycosylation profile and aggregate levels as critical quality attributes and their periodic monitoring throughout the culture using off-line analysis

https://database.ich.org/sites/default/files/Q10%20Guideline.pdf and ISA88

Per ICH: A planned set of controls, derived from current product and process understanding, that assures process performance and product quality. Control strategy can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. Per ICH: Quality risk management is used to establish the control strategy. This can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in process controls, finished product specifications, and the associated methods and frequency of monitoring and control. The control strategy should facilitate timely feedback / feedforward and appropriate corrective action and preventive action.

ControlStrategy(x) → PlanSpecification(x) ∧ ∃y((ProcessParameterSpecification(y) ∨ QualityAttributeSpecification(y) ∨PerformanceIndicatorSpecification(y)) ∧ hasContinuantPartAtAllTimes(x, y))

true

plan specification consisting of one or more specifications of methods and technologies that prescribe the monitoring or regulation of process parameters, quality attributes, and process performance indicators associated with a particular process and its resulting material product

There are insufficient constructs in this release to fully capture the structure of a control strategy.

if x is a 'control strategy', then x is a 'plan specification' that 'has continuant part at all times' some y, where y is either a 'process parameter specification', a 'quality attribute specification', or a 'performance indicator specification'

material quality plan A material quality plan for particular chromatography resin prescribes synthesis process controls, intermediate and final QC testing, and release criteria to ensure the resin meets defined binding capacity, particle size distribution, and metal impurity limits. It includes in-process monitoring of pH and temperature during functionalization, validated leachables testing, and visual inspection.

1) At least one process prescribed by some part of the quality plan has to be a measurement process 2) The processes embedded in the quality plan typically include testing, inspection, characterization

MaterialQualityPlan(x) → PlanSpecification(x) ∧ ∃a(PlanSpecification(a) ∧ ∃m(MeasurementProcess(m) ∧ prescribes(a, m)) ∧ hasContinuantPartAtAllTimes(x, a)) ∧ ∃q(QualityAttributeSpecification(q) ∧ hasContinuantPartAtAllTimes(x, q)) ∧ ∃p(PlannedProcess(p) ∧ (∃pp(ProductProductionProcess(pp) ∧ (precededBy(p, pp) ∨ occurrentPartOf(p, pp) ∨ isTemporallyOverlappedBy(p, pp))) ∧ prescribes(x, p)))

true

planned specification that prescribes the processes needed to ensure that a material product meets the required quality objectives

There are insufficient constructs in this release to fully capture the structure of a material quality plan

if x is a 'material quality plan', then x is a 'plan specification' that 'has continuant part at all times' some 'plan specification' a that 'prescribes' some 'measurement process', and 'has continuant part at all times' some 'quality attribute specification', and 'prescribes' some 'planned process' p that either 'precedes', is an 'occurrent part of', or 'is temporally overlapped by' some 'product production process'

material sample A 10 mL aliquot of bioreactor culture collected during mid-log phase for cell viability analysis; a pre-filled vial of harvested supernatant taken from a chromatography pool for impurity testing; a powder sample taken from the middle of a drum of API to test for uniformity of composition; a tablet randomly selected from a production batch during compression for hardness testing

MaterialSample(x) ↔ MaterialEntity(x) ∧ ∃s(SamplingProcess(s) ∧ isSpecifiedOutputOf(x, s))

material entity that is the specified output of a sampling proces

every instance of 'material sample' is defined as exactly an instance of 'material entity' that 'is specified output of' some 'sampling process'

monitoring plan A monitoring plan for the tablet compression process prescribes in-process testing of tablet samples every 30 minutes or every 50,000 tablets. It targets weight (540–560 mg), hardness (8–12 kp), thickness (4.8–5.2 mm), and disintegration time (<15 minutes). The responsible agents are the production operator and QC technician;An environmental monitoring plan for the production area prescribes continuous monitoring of temperature (18–25 °C) and humidity (45–65%) using data loggers. The responsible agent is the facilities technician; A bioreactor monitoring plan prescribes continuous monitoring of pH, dissolved oxygen, temperature, and agitation speed during a cell culture process.

A monitoring plan typically specifies the measurement frequency, target metrics, and the responsible agent.

MonitoringPlan(x) → PlanSpecification(x) ∧ ∃y(MonitoringProcess(y) ∧ prescribes(x, y))

true

plan specification that prescribes some monitoring process

There are insufficient constructs in this release to fully capture the structure of a monitoring plan.

if x is a 'monitoring plan', then x is a 'plan specification' that 'prescribes' some 'monitoring process'

monitoring process process monitoring UV absorbance and conductivity monitoring during column loading; continous monitoring of temperature and humidity in a clean room; Tablet weight is measured in-line every 30 minutes during compression using an integrated balance; During a fed-batch cell culture process, at-line nutrient monitoring is performed using a Nova BioProfile® FLEX analyzer to measure glucose, lactate, glutamine, and ammonia levels; Flow rate is continuously monitored during tangential flow filtration to ensure consistent membrane performance

https://www.biopharminternational.com/view/monitoring-biopharmaceutical-processes-present-and-future-approaches

1)Each monitoring process is an execution of a monitoring plan that prescribes it 2) In case a monitoring process is responsible for monitoring the attribute/parameter/indicator in multiple processes (e.g., multiple unit operations) it is a part of the 'larger process' which has the 'occurrent part' the unit operations and it does not imply that it is an occurrent part of the unit operations themselves".

MonitoringProcess(x) ↔ PlannedProcess(x) ∧ ∃m(MeasurementProcess(m) ∧ hasOccurrentPart(x, m)) ∧ ∃p(PlannedProcess(p) ∧ occurrentPartOf(x, p)) ∧ ∃mp(MonitoringPlan(mp) ∧ prescribedBy(x, mp))

planned process that is a part of another planned process and that consists of one or more observation or measurement processes in which a particular attribute (specifically dependent continuant or temporal region or process characteristic or process profile) of some entity of interest is measured or observed

every instance of 'monitoring process' is defined as exactly an instance of 'planned process' that 'has occurrent part' some 'measurement process', is 'occurrent part of' some 'planned process', and is 'prescribed by' some 'monitoring plan'

sample plan Merck KGaA sampling plan sampling strategy Sampling plan that prescribes in-process sampling on Days 5, 7, and 9 for glycan profiling of the expressed monoclonal antibody; Sampling plan that prescribes post-harvest sampling to assess product titer and host cell protein levels before downstream purification; Sampling plan that prescribes manual collection of 20 tablets per batch for disintegration and hardness testing in the QC lab; Sampling plan that prescribes taking an aliquot from every third eluate fraction during protein A chromatography for titer and impurity analysis (HCP and DNA)

https://itl.nist.gov/div898/handbook/ppc/section3/ppc33.htm

1) A sampling plan in the context of production and quality management refers to a documented strategy that defines how, when, and how often samples are to be taken from materials, products, or processes for testing or inspection. 2) Key aspects of a sampling plan include: Frequency: Specifies how often samples should be taken (e.g., every batch, every tenth delivery, or at regular time intervals). Sample Size: Defines the number or quantity of items to be sampled at each interval.

SamplePlan(x) → PlanSpecification(x) ∧ ∃y(SamplingProcess(y) ∧ prescribes(x, y))

true

plan specification that prescribes how, when and how often samples are to be taken during a particular process

There are insufficient constructs in this release to fully capture the structure of a sample plan

if x is a 'sample plan', then x is a 'plan specification' that 'prescribes' some 'sampling process'

sampling process material sampling process Merck KGaA Sampling process in which a technician disinfects the sampling port of a 2000 L CHO cell culture bioreactor with 70% ethanol, withdraws 15 mL of culture using a sterile syringe, discards the first 2 mL, collects the remaining 10 mL into a labeled sterile vial, and seals it for downstream analysis; Sampling process in which an operator manually collects 5 tablets from the compression chute using a stainless-steel scoop, places them into a labeled clean glass container, records the batch number and time, and seals the container for later analysis

https://www.sciencedirect.com/topics/engineering/sampling-process

A technician places a labeled sample vial in a cold box and transports it to the analytical lab (this is sample transport and not sampling itself); An operator fills final product into vials for distribution; A lab analyst measures glucose concentration in a sample using a Nova BioProfile® FLEX analyzer (this is an analysis conducted after the sampling and not the sampling itself)

sampling might involve conditioning (e.g., cooling, filtering, putting in a specific container), preparing, and documenting the sample The sampling process is designed to ensure that the test results subsequently conducted on the sample are reliable and representative of the overall material or product, supporting effective quality control and decision-making.

SamplingProcess(x) → PlannedProcess(x) ∧ ∃m(MaterialEntity(m) ∧ hasInput(x, m)) ∧ ∃s((MaterialEntity(s) ∧ (memberPartOfAtSomeTime(s, m) ∨ properContinuantPartOfAtSomeTime(s, m))) ∧ hasSpecifiedOutput(x, s)) ∧ ∃p(SamplePlan(p) ∧ prescribedBy(x,p))

true

planned process of selecting and collecting a limited amount or number of some material entity in a manner which ensures it is representative of the input material entity

There are insufficient constructs to create a set of necessary and sufficient conditions. In particular, pattern and all the constructs for representing that the sample is taken in a manner which ensures it is representative of the input are missing

if x is a 'sampling process', then x is a 'planned process' that 'has input' some 'material entity' m and that is 'prescribed by' some 'sampling plan' p and 'has specified output' some s, where s is either a 'member part of at some time' or a 'proper continuant part of at some time' of m