Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5886_Библиотеки_им_академика_М_И_Перельмана.pdf
X
- •Foreword
- •Preface
- •Acknowledgements
- •Contents
- •Contributors
- •About the Editors
- •1.2.2.3 Progeria
- •1. Bioprocessing, Bioengineering and Process Chemistry in the Biopharmaceutical Industry: Using Chemistry and Bioengineering to Improve the Performance of Biologics
- •1.1 Introduction
- •1.2.2.2 Cystic Fibrosis
- •1.3.2.1 ADC Drugs
- •1.4 Top 25 Best-Selling Drugs
- •1.5.1 An Overview
- •1.5.2 Synthetic Biology
- •1.5.8 Biopharmaceutical Regulatory CMC
- •1.5.9 Technology Transfer
- •References
- •2.1 What Is Synthetic Biology?
- •2.6 CAR-T Cell Therapies
- •2.7 Conclusion
- •References
- •3.1 Introduction
- •3.2.1 Oligonucleotide Synthesis
- •3.2.1.1 Early Synthetic Chemistries
- •3.2.2 Solid Supports
- •3.2.3 Modern Oligo Synthesis Platforms
- •3.3 Gene Synthesis
- •3.3.1 Early DNA Assembly Methods
- •3.3.2 Array-Based Gene Synthesis
- •3.4 New Discovery Bottleneck
- •3.4.1.1 Hybridoma Technology
- •3.4.1.2 Phage Display Technology
- •3.4.1.3 Synthetic Antibody Library Construction
- •Semi-Synthetic Libraries
- •Fully Synthetic Libraries
- •3.5 Perspectives
- •References
- •4.1 Introduction
- •4.2.1 Batch
- •4.2.2 Fed-Batch
- •4.2.4 Hybrid Processes
- •4.2.7 Dynamic Perfusion Processes
- •4.3.2 Glucose Limitation
- •4.4.1 N-1 Perfusion
- •4.4.3 Linked Bioreactors
- •4.5 Process Analytical Technology
- •4.6 Single-Use Bioreactors (SUBs)
- •4.7 Conclusions
- •References
- •5.1 Introduction
- •5.2.1 Molecular Format Considerations
- •5.2.1.1 The Charge-Based Electrostatic Approach
- •5.2.1.2 The Knob into Hole Approach
- •5.2.2.1 Stable CHO Host Cell Integration System—Random or Targeted?
- •5.2.2.2 Expression Vector Considerations
- •5.2.2.3 Cell Line Screening Strategy Considerations
- •5.3.1 Upstream Process Development
- •5.3.2 Downstream Process Development Considerations
- •5.3.2.1 Unique Impurity Challenges
- •5.3.2.2 Stability Concerns
- •5.5.2.1 H/H Removal
- •5.5.2.2 HMMS Removal
- •References
- •6.1 Introduction
- •6.2.1 N-Linked Glycosylation
- •6.2.2 O-Linked Glycosylation
- •6.2.3 Glycosaminoglycan Synthesis
- •6.3.1 Mannosylation
- •6.3.2 Fucosylation
- •6.3.3 Galactosylation
- •6.3.4 Sialylation
- •6.5 Glycoengineering
- •6.5.1 Manipulating Heterogeneity
- •6.5.2 Manipulating Sialylation
- •6.5.2.1 Increasing α-2,6 Sialylation
- •6.5.3 Manipulating Fucosylation
- •6.5.4 Manipulating Branching
- •6.6.1 Temperature
- •6.6.2 pH
- •6.6.3.2 Amino Acids
- •6.6.3.3 Glycosaminoglycan Production
- •6.6.4 Culture Additives
- •References
- •7.1 Introduction
- •7.1.1 AAV Gene Therapy
- •7.3.1 Humoral Immunity
- •7.3.2 Cell-Mediated Immunity
- •7.4 Conclusion
- •References
- •8.1 Introduction
- •8.2 mRNA Vaccines
- •8.2.1 Background
- •8.2.2 Production Process
- •8.2.2.2 Production
- •8.4.1 Background
- •8.4.2 Production Process
- •8.4.2.2 Production
- •8.4.2.3 Viral Inactivation
- •8.5 Protein-Based Vaccines
- •8.5.1 Background
- •8.5.2 Production Processes
- •8.5.2.1 NVX-CoV2373 (Novavax)
- •8.3 Viral Vectors
- •8.3.1 Background
- •8.3.2 Production Process
- •8.3.2.2 Production
- •8.4 Whole Inactivated Virus Vaccines
- •8.5.2.2 CoVLP (Medicago)
- •8.5.2.3 EpiVacCorona (Vector Institute)
- •8.7 Conclusions
- •References
- •9. CAR-T Bioprocessing
- •9.1 Introduction
- •9.2.1 Introduction
- •9.2.2 Lentiviral Vector Design
- •9.2.5 Upstream Bioprocessing
- •9.2.6 Downstream Bioprocessing
- •9.3 Cell Product Bioprocessing
- •9.3.1 End-to-End Systems
- •9.3.4 Activation
- •9.3.6 Cell Expansion
- •9.3.8 T-Cell Cryopreservation
- •References
- •10.1.1 What Is CRISPR?
- •10.1.4 Mechanism Behind CRISPR Gene Editing
- •10.2.1 Creating Gene Knockouts
- •10.2.2 Creating Gene Knock-Ins
- •10.2.4 CRISPR Screens
- •10.3.1 Derivative Technologies
- •10.4.2 Delivery Methods
- •10.6.2 TCR Engineered T Cell Therapy
- •10.6.3 Chimeric Antigen Receptor T Cell Therapy
- •10.9.2 Safety Considerations
- •References
- •11.1 Introduction
- •11.1.2 Categories
- •11.2 Current Status
- •11.2.1 Approved Products
- •11.2.2 Market
- •11.3 Design
- •11.3.1 Building Blocks
- •11.3.2 Linkers
- •11.3.3 Oligomerization
- •11.3.3.1 Monomer
- •11.3.3.2 Dimer
- •11.3.3.3 Trimer
- •11.3.3.4 Tetramer
- •11.3.3.5 Pentamer
- •11.3.3.6 Hexamer
- •11.3.3.7 Octamer
- •11.3.4 Orientation
- •11.3.5 Protein Engineering
- •11.3.6 Immunogenicity
- •11.4 Manufacturing
- •11.4.1 Upstream
- •11.4.2 Downstream
- •11.4.3 Glycosylation
- •11.4.4 Aggregation
- •11.4.5 Analytics
- •11.5 Therapeutic Concepts
- •11.5.1 Half-Life Extension
- •Albumin Fusions
- •Fc Fusions
- •Transferrin Fusions
- •Repetitive Peptide Fusions
- •Glycosylated Peptides
- •11.5.1.3 Aggregate Forming Peptides
- •11.5.2 Targeting Functions
- •11.5.3.1 Fc Domain Receptor-Mediated Toxicity
- •11.5.3.2 Toxins
- •11.5.3.3 Immunocytokines
- •11.5.3.4 Human Enzymes
- •11.5.3.5 Apoptosis Induction
- •11.6 Summary
- •11.7 Future Perspectives
- •References
- •12.1 Introduction
- •12.2 ADC History
- •12.3 Target Selection
- •12.4 Antibody Selection
- •12.6 ADC Technology
- •12.7 ADC Clinical Development
- •12.8.1 Mylotarg
- •12.8.2 Adcetris
- •12.8.3 Kadcyla
- •12.8.4 Besponsa
- •12.8.5 Polivy
- •12.8.6 Padcev
- •12.8.7 Enhertu
- •12.8.8 Trodelvy
- •12.8.9 Blenrep
- •12.8.10 Zynlonta
- •12.8.11 Tivdak
- •12.9 Concluding Remarks
- •References
- •13.1 Introduction
- •13.2 Gemtuzumab Ozogamicin
- •13.3 Gemtuzumab Antibody
- •13.4 Calicheamicin
- •13.7.3 Isolation of N-Acetyl Calicheamicin
- •13.10 Conclusions
- •References
- •14.1 Introduction
- •14.2.1 Antibody Generation
- •14.3.1 Structure Prediction
- •14.3.2 Biophysical Properties
- •14.3.3 Hydrophobicity
- •14.3.5 Isoelectric Point (pI)
- •References
- •15.1 Introduction
- •15.2 ADA Program Development
- •15.2.3 Project Approach
- •15.2.4 Model Library
- •15.3 Case Study
- •15.3.3 Hypothesis Generation
- •15.3.5 Feature Engineering Example
- •15.3.7 Model Insights
- •References
- •16.1 Introduction
- •16.1.1.1 United States
- •16.1.1.2 European Union
- •16.1.2 Global Markets
- •16.4.1 United States FDA
- •16.4.2 European Medicines Agency (EMA)
- •16.4.3 The World Health Organization
- •References
- •17.1 Introduction
- •17.3.1.2 Clone Selection

440
J. Luo et al.
information and the prior knowledge via Bayes’ theorem. Bayes’ theorem describes
the conditional probability of an event based on data as well as prior information or
beliefs about the event or conditions related to the event.
There are increasing numbers of empirical studies that have demonstrated
Bayesian methods are explicitly selected to better accommodate reduced sample
sizes, ranging from life science, psychology, exercise science, cross-cultural studies, and prevention science [8, 9]. Among many Bayesian methods, a framework
that combines cause and effect diagrams with Bayesian belief networks (BBNs) to
estimate causal relationships could be leveraged for the biomanufacturing process
[10]. The framework translates qualitative insights from a cause-and- effect diagram
into a closed-form relationship between inputs and outputs utilizing BBN models,
simulation, and regression. The framework starts with a typical Fishbone diagram to
construct a causal network, then estimate the probability of problem occurring using
BBN and probabilistic elicitation, and nally identify the vulnerabilities of the network through simulation. This allows investigation practitioners to identify critical
root causes of a given problem when data collection activities can often consume
valuable resources or events occurring at a low frequency with a high risk of severity.
When a large enough data set is generated at a commercial scale, ADA is a tool
that can complement traditional univariate monitoring programs to bolster knowledge, improve capability, and optimize bioprocess performance. Within the data
science community, the use of statistical modeling to reach conclusions from data
can be divided into two separate “cultures” [11]. One assumes that the data are generated by a given stochastic data model. The other uses algorithmic models and
treats the data mechanism as unknown. Because data collected during commercial
manufacturing (where the process runs at or close to the target as designed) may
involve complex systems with unknown physical, chemical, or biological mechanisms, signals from stochastic data models may be weak and difcult to interpret.
Therefore, algorithmic models using ADA may elucidate previously undetected
relationships between inputs and outputs, and hold promise to gain actionable
insights and knowledge to better understand, predict, and control sources of variation in a bioprocess [12].
While there are many ADA techniques available, two types of ADA models
could be built based on different biomanufacturing applications, namely diagnostic
(or root cause) models and predictive models. Both models provide information to
gain process understanding. Specically, the root cause model (explanatory model)
focuses on actionable inputs for process troubleshooting and improvement, and
makes sure the insights from the “black box” models can be explained. When the
model focuses on actionable process inputs, the newly identied cause could either
be veried through small-scale lab studies or large-scale process changes and subsequently monitoring. The predictive model uses all available inputs for output prediction, regardless of the model’s interpretability. This could be very helpful in
making early and/or real-time forward process decisions. It could also be extremely
useful if there is an intrinsic correlation between process outputs. Using easy to

15 Advanced Data Analytics Application inBiomanufacturing Processes
detect process output to predict the hard-to-measure process output could signicantly improve the process efciency.
With the help from an external consultant company, an internal ADA program
including a cross-functional team, IT infrastructure, data engineering technique,
data visualization and modeling methodology is established. This article will
describe the ADA program developed in-house and the established procedure to
conduct the analysis. Specically, a case study to gain additional insights for an
intractable cell culture performance problem is conducted. The model insights, the
observed and predicted benet based on the model outcome, are discussed. The
importance of building ADA capabilities to enable more efcient and reliable bioprocesses is also discussed.
441
15.2 ADA Program Development
With the help from McKinsey/Quantum Black (McK/QB) consultant rm, an inhouse ADA program was developed and established. The program includes a crossfunctional team, established environmental and tool, business process to run
individual projects (use cases), and a library of models. In addition, data standardization, digitization, and data sharing are key factors to ensure the success of the
program.
15.2.1 Building aCross-Functional Team forADA Program
The team composed of global and local cross-functional experts is formed. The
team members and their corresponding responsibilities are as follows:
• Program leader: to set up program governance and to manage ADA engagement
• Project leader/translator: to set and track progress, to provide guidance/steering
to the team, and to coordinate and facilitate interactions across disciplines
• Technical subject matter experts (SMEs): to share expertise and help with
problem- solving and to help dene root causes/drivers based on insights from
analytics
• Data engineer (DE): to work with source system owners to make data available
and to cleanse and link data in preparation for analysis
• Data scientist (DS): to dene the analytic approach and execution of analysis
and to interpret model results
• Information technology (IT)/technical liaison: to provide information on techni-
cal architecture, and to establish tools and standard, and to continuously opti-
mize and quality check for development and deployment

442
J. Luo et al.
15.2.2 IT Infrastructure andTools
New environments and tools are established for the ADA program (Table15.1). The
platform is built on the Google Cloud Platform (GCP). Google Cloud Storage,
BigQuery, and Dataproc are often used for data storage, data exploration, and highperformance distributed computing, respectively. Python is used as the primary programming language for data analysis. The Data Pipeline was introduced and built
Table 15.1 IT infrastructure and tools used in ADA program
Environment /
tool Description Key capabilities built
Google Cloud
Platform
(GCP)
Dataproc Analytics engine for large-
Google Cloud
Storage (GCS)
BigQuery Cloud data warehouse Load/Query data in BigQuery
Python A programming language Develop and improve the codebase, follow
Jupyter
Notebook
Kedro An open-source Python
GitHub Version control development
JIRA Agile sprint planning tool Manage tasks and collaborate with the virtual
Conuence Remote-friendly team
https://Cloud.google.com
https://spark.apache.org/
https://Python.org
https://Jupyter.org
https://kedro.readthedocs.io
https://github.com/
https://www.atlassian.com/software/conuence
A suite of cloud computing
services that runs on the same
infrastructure offered by
Google
scale data processing
Worldwide cloud storage that
can retrieve any amount of data
at any time
Open-source web application
for creating and sharing
documents that contain live
code, equations, visualizations,
and narrative text
framework for creating
reproducible, maintainable and
modular data science code
platform
workspace
Learn/practice/improve on working in GCP
(cluster, codebase, notebook, etc.). Run data
engineering pipeline and data science
analytical modules in GCP.Master basic
DevOps (Spinning up a cluster, Terminal
SSH, basic Linux commands)
Use Dataproc and Pyspark for distributed
computing
Ingest data into the GCS environment
good coding practices, peer code review, test.
Perform data analysis in CLI/Jupyter
Notebooks
Understand the Data Pipeline concept
Create raw layers, intermediate layers,
primary layers, feature layers, model input
table of the data engineering pipeline
Understand Git workow. Update data
engineering pipeline with Git
team in agile ways. Implement SCRUM and
work in sprints as foundations
Use as a team workspace, knowledge sharing,
and collaboration tool

15 Advanced Data Analytics Application inBiomanufacturing Processes
443
using Kedro, an open-source framework for creating reproducible, maintainable,
and modular data science code. All codes are version controlled in Github. Jupyter
Notebook is used to support data analysis and result sharing. The project is operated
in an agile paradigm running sprints using JIRA.All the knowledge and documentation are stored in Conuence as a team workspace.
15.2.3 Project Approach
The program is executed through individual use cases. Analytics problem-solving
requires translating a business problem (use case) into an analytics problem and
solving it through an iterative process of hypotheses generation, exploratory analysis, and feature creation. Each project could be separated into ve phases: preparation, initial analysis, model iteration, translating to actionable insights, and model
outcome conrmation. Table15.2 summarized the detailed deliverables from each
phase. Figure15.1 showed a map of the project approach to data transformation
processes (i.e., data pipeline). Throughout the project, translators, Des, and DSs
worked together with the process SMEs to dene hypotheses and select variables/
features (model inputs), and to prioritize the work based on the hypothesis and data
availability. Among different use cases, the continuous improvement on the overall
program platform and the model methods are important, and the reusability of the
pipeline built from one use case to another should be maximized.
Table 15.2 ADA project phase deliverables
Phase Deliverable
Preparation Select use case
Align on scope and denition
Develop detailed execution plan
Set up the technical execution environment
Dene initial hypothesis
Identify/prioritize data source based on initial hypotheses
Align on people/capabilities and roles
Initial analysis Dene model outputs
Model selection
Data ingestion (data extract from data sources)
Data clean/transformation & quality check (link data based on
hypotheses)
Feature creation
Exploratory data analysis (EDA)
Model development and
iteration
Model insights Build graphical representations of the Insights gained. Develop
Insights conrmation Conrm the insight by further lab study, additional monitoring after
Build model/Analytical engine
Iterate could be based on new data sources, new hypotheses, or
rened features
reports for a wide range of users
proposed change implementation

444
J. Luo et al.
Fig. 15.1 A map of the project approach and data transformation processes (i.e., data pipeline)

15 Advanced Data Analytics Application inBiomanufacturing Processes
445
15.2.4 Model Library
Machine learning is used to teach machines how to handle the data more efciently.
Simply, machine learning can be better understood as “learning from data” [13].
There are two types of machine learning algorithms, unsupervised and supervised
[14]. Unsupervised learning uses machine learning algorithms (e.g., K-means,
PCA) to analyze and cluster unlabeled data sets. These algorithms discover hidden
patterns in data without the need for human intervention (hence, they are “unsupervised”). It is mainly used for clustering, association, and dimensionality reduction.
Supervised learning is a machine learning approach that’s dened by its use of
labeled datasets. These datasets are designed to train or “supervise” algorithms into
classifying data or predicting outcomes accurately. Using labeled inputs and outputs, the model can measure its accuracy and learn over time. Currently, supervised
machine learning methods are primarily used in the ADA program, which includes
Linear regression, Lasso, Decision trees, Random forest, and Gradient boosting.
Lasso, Random forest, and Gradient boosting are chosen because of their feature
selection properties. Linear regression and Decision trees are used as the linear and
nonlinear benchmarks for model comparison. Other methods such as generalized
random forest have been studied and applied as appropriate.
15.3 Case Study
15.3.1 Case Study Selection forADA Modeling
The goal of the case study was to build a model to explain variation and identify
actionable insights for a fed-batch Chinese hamster ovary (CHO)-based bioprocess
process (Fig.15.2).
Fig. 15.2 Process owchart from seed train to large-scale cell culture process, including raw
material and medium prep. HTST refers to high temperature short time

446
J. Luo et al.
Many factors were considered for the case study selection process, such as sample sizes, the variability of the process output, the impact on business, the variability
of data sources, data accessibility, and process knowledge. For example, to develop
a meaningful ADA model, it was suggested to have a manufacturing history of at
least 100 large runs. Second, if the variation in interest is observed throughout the
process history, it may be a more suitable use case. Since cell culture processes typically run in campaign mode, the campaign-to-campaign (raw material variability)
or thaw-to-thaw variability is a common variation observed in bioprocess. Without
variation observed in the historical data, there is nothing for the ADA model to
optimize. In addition, where and how data were generated, captured, and stored will
determine the data availability, data quality, and amount of effort for data engineering.
In this specic case, the selected process (Process A) generated more than 300
runs over the manufacturing history. As shown in Fig.15.3, 95% of all runs have
normalized titer ranging from 0.77 to 1.22. Among the total observed variation, the
within-campaign variation takes about 52%, and the between-campaign variation
takes 48%. Table15.3 summarizes an example on process inputs and output for cell
culture process. For process input, in addition to the typical primary process parameter for characterization, the associated control strategy and secondary process
parameters should also be included in the analysis.
The total number of runs available and relatively high historical variability made
the process a good candidate for the analysis. In addition, most site data sources
existed in digital format except for a subset of raw material release test results and
paper-based executed batch records. The data availability will shorten the data preparation phase and enable more rapid problem solving. Based on the aforementioned
Fig. 15.3 Normalized historical titer performance of Process A by campaign (shown in different
colors and separated by vertical lines) and thaw line (shown in different symbols). C#
Campaign number

15 Advanced Data Analytics Application inBiomanufacturing Processes
Table 15.3 Upstream process inputs and outputs
Process input
Attribute Attribute description Associated control/parameter
Thaw Time Bank storage, transfer operation
Temp Setpoint, shift, shift timing Control loop, tank vs jacket temp
pH Setpoint, shift, shift timing Deadband, probe calibration
DO Agitation, sparge, overlay
ow rates
Medium Concentration Medium prep/transfer operation, medium
Feed Number, concentration,
volume, timing
Inoculation
density
Culture duration Time
Cell age Seed train maintenance, # of
Glucose Min/Max concentration Addition strategy
Antifoam Addition strategy
Process output
Category Attribute description
Cell state Viability, integrated growth (growth rate)
Metabolite Lactate, ammonium, pCO
Productivity Titer
Purity Charge variants, size distribution, glycosylation
Specic
modication
Impurity CHOP, DNA, sequence variants
Potency Potency by Anti-Proliferation, potency by Antibody-Dependent Cellular
Contaminants Bioburden, endotoxin, virus, mycoplasma
Viable cell density
nonselective passage
Deamidation, glycation, oxidation
Cytotoxicity (ADCC)
Aeration strategy
composition, raw material release
specication
Medium prep/transfer operation
Solera operation, scale up strategy
2
447
factors, combined with a positive business value associated with understanding or
reducing the performance variation, Process A was selected for the case study.
15.3.2 Data Sources Identication
A holistic review of the manufacturing process was conducted, and 11 data sources
were identied that store manufacturing information. The data in 11 data sources
were stored or extracted in different formats, such as Oracle databases, time-series
data historian, scanned paper copy, and Microsoft Excel le.

448
J. Luo et al.
15.3.3 Hypothesis Generation
The generation of the hypotheses is a collaborative effort between the business, the
analytical team, and domain experts. Hypotheses are at the heart of every project
and inform how data is ingested and how analytics is performed. In this use case,
more than 100 hypotheses were generated and prioritized among process, raw material, and test method areas.
Based on the importance of the hypothesis and data availability, data ingestion
process was prioritized. For example, a key hypothesis for culture performance
variation was associated with raw material variation [15]. Therefore, incorporating
raw material test results into the ADA model was required. However, because raw
material release test information was paper based, digitizing raw material data
became a top priority early in the project. In addition, the analysis is to identify factor to further improve titer/reduce titer variability; only process inputs are included
in the model.
15.3.4 EDA andFeature Engineering
Once the raw data were available, data was cleaned, rearranged in smaller tables,
and data from different tables were joined as a pipeline. Then data was ready for
exploratory data analysis (EDA) and feature engineering. Once the feature was created, all features were joined to a master data table, and a model could be built based
on the master data. Prior to running the model, Variance Ination Factor (VIF) was
used for feature selection; this is to deal with multicollinearity between features and
achieve more stable explanations of models. A VIF of 5 was used as a threshold for
feature selection, which means the feature will be removed from model input if it
can be explained 80% by other features. Based on the EDA or the initial model
outcomes, additional data might be added to the pipeline or additional features
could be created for model updates. As mentioned above, the overall pipeline was
built on Kedro using Python [16].
15.3.5 Feature Engineering Example
For mammalian cell culture, pH setpoint and pH control are known factors to impact
cell growth and productivity [17, 18]. Therefore, it is expected to build features
based on pH information. Features created from pH information described below
show an example of the data ingestion process. The online pH (PI data historian) for
one inoculum train stage is the raw data from the manufacturing process. In addition
to the culturing phase, the pH information before (medium only) and during inoculation (transfer cells from the previous culture to medium), and transfer out

15 Advanced Data Analytics Application inBiomanufacturing Processes
449
(inoculation for the next stage) could be extracted as different phases from data. In
addition, during the culturing phase, the pH experienced a shift, which is due to the
interaction between cell growth and pH control deadband. Therefore, pH during
culture could be further partitioned into before, during, and after the shift. During
culture transfer out, pH control was turned off, and the probe would be exposed to
air at a certain level (tank-specic information). Linking other time-series data (e.g.,
tank volume or weight) and equipment information is, thus, required to get the
transfer-out information. With this detailed process knowledge, the features were
built for pH in one inoculum train culture stage as shown in Table15.4. As part of
feature generation, EDA to review pH effect is performed to verify the correction of
data ingestion and linkage and to understand if there is any effect.
Table 15.4 Data ingestion process for online pH in one inoculum train
Steps pH example Chart example
Raw data pH in one inoculum train stage
Intermediate
data
Primary layer Based on pH and weight trend,
Feature For each pH phase, explore the
a
Might go back to raw data based on initial data extraction frequency
Associate pH with equipment
data and tank weight (kg) to
identify different phases of pH
separate pH trend in one culture
stage into six different phases
1: medium batch
2: inoculation
3: pH at the top of deadband
4: pH transition from top to
bottom of dead band
5: pH at the bottom of deadband
6: Transfer out
pH: min, max, average, 25, 50,
75 percentile of pH
For each pH phase, explore the
duration, the ratio of each
duration to overall duration
For culturing phase, explore any
pH excursion: spike, change due
to online/ofine adjustment,
a
etc.
a
a
Max phase 3 pH for all runs in one inoculum
train stage
Соседние файлы в папке Библиотека им академика М.И. Перельмана
