Industrial Bioprocessing Simulation and Modelling The document discusses industrial bioprocessing, simulation, and modeling. It provides an overview of bioprocessing history and applications. Process simulation and modeling tools are used to optimize efficiency without extensive experimentation. Downstream processing aims to purify products through techniques like filtration. Process design considers product properties and impurities. Scale-up requires maintaining parameters like bed height and velocity. Career opportunities exist in engineering and science roles in biopharmaceutical industries, with salary packages ranging from 3.25-8 LPA depending on level.

1. Industrial Bioprocessing
Simulation and
Modelling
Presented by
Shubham A. Chinchulkar

2. Flow of presentations
Introduction to bioprocess, simulation, and modeling
Downstream Process Design, Scale-Up Principles, and
Process Modeling
Career Scope
Where can you get the jobs
What will be the salary package?

3. Introduction

4.  It is a specific process that uses complete living cells or their components to obtain desired products
 Industrial bioprocessing is mainly deals about designing, developing, manufacturing of products in
pharmaceuticals, agriculture, fed, food, and polymers
The first bioprocess complete
description
2400 BC
Industrial production of Antibiotics
1940
Industrial production of rHuman
Insulin in E.coli
1982
STR for mammalian cell culture
2000

5. Industrial
Bioprocessing
Mid 19th century
Yeast
Solvents
Organic acids
Amino acids
End 19th century
Antibiotics
Enzymes
Vaccine
Biopolymers
Early 20th century
Biopharmaceuticals
Monoclonal antibodies
Biodiesel
Recombinant proteins

6. Process Simulation and Modeling
Maximizing profits by operating the most efficient process is the primary goal of all industrial
bioprocessing operations
To help create efficient operations, companies use process simulation, which is the application of a
range of software tools to analyze complete processes, not just single unit operations
Process engineers and scientists use simulation models to investigate complex and integrated
biochemical operations, without the need for extensive experimentation
Simulation tools can be used at any stage of process development
These tools tackle a range of tasks, including creating process flow diagrams, generating material
and energy balances, determining equipment sizing, and estimating capital and operating costs

7. • The minimum requirements for a biochemical process simulator are the ability to
handle batch as well as continuous process and the ability to model the unit operations
that are specific to bioprocessing
• Aspen Plus (Aspen Technology): It was first tool. This used to carry out the material
and energy balances, estimate the size, cost of equipment, and perform the economic
evaluation. It is less commercially successful because it was designed that normally
operate only in batch mode
• BATCHES: It is having application in pharmaceutical, food, and in biochemical
processing. It is useful for fitting a new process into an existing facility and analyzing
resource demand as a function of time
• BioPro Designer: It helps in handling of materials and energy balance, equipment
sizing and costing, economic evaluation, environmental impact assessment, process
scheduling, and debottlenecking of batch and continuous processes

8. DOWNSTREAM
PROCESS DESIGN,
SCALE-UP
PRINCIPLES
PROCESS
MODELING

9.  Downstream processing is the recovery and purification of products with proper treatment
 It includes steps like cell separation, filtration, product recovery, extraction of product and purification
and then treatment of product by chemical, physical and biological means
ICH Q8 guidelines - the aim of pharmaceutical development is to design a quality product and
the manufacturing process to deliver the product in a reproducible manner
Developed process must be validated to ensure that the produced product meets the safety requirement for
human administration throughout the whole product lifecycle
Validation - collection and evaluation of data, from development through to commercial production
It establishes scientific evidence for process consistency

10. Validation
Stage 1—Process
Design
Stage 2—
Process
Qualification
Stage 3—
Continued
Process
Verification
Commercial manufacturing process is
defined during this stage based on
knowledge gained through development
and scale-up activities
During this stage, the process design is
evaluated to determine if the process is
capable of reproducible commercial
manufacturing
Ongoing assurance is gained
during routine production that
the process remains in a state of
control

11.  Process should be that robust and consistent
 In reality during process development changes need to be done during different stages:
 Costly changes of the process and concomitant critical attributes of the product will result in risk for
delays
or even failure of the project
 Efficient and robust process design can help mitigate the risk of change and delay on the overall
process
a. Materials for preclinical evaluation
b. Materials for clinical evaluation (stage I/II)
c. Materials for stage III clinical evaluation or large scale
Process
design
Process
development
Process
control

12. Three Core Elements of Process Design Framework
Element Examples Comment
Selection of industrial tools Cell lines
Raw materials
Consumables
Documented evidence, internal
and vendor audits, manufacturing
experience
Selection of technologies and
methods
Analytical methods
Cell separation methods
Purification methods
Viral clearance
Product and impurity profiles, risk
analysis, heuristic designs,
experimental
performance evaluation
Integration Use of one buffer system for multiple
steps
Column packing
Use of disposables
Reduction of time-consuming
associated
activities, eliminate non-
productive steps.

13.  Process design begins with expression system chosen, and with the information about the target molecule
acquired
 Target molecule information -
a. Physicochemical and biological properties
b. Stability under the chemical and physical conditions
c. Type of impurities
 Factors affecting the stability of protein-based target molecules include the presence of protease, protein
concentration, pH, temperature, co-solvents, salts (concentration and type), co-factors, and redox potentials
 pH, salt concentrations, additives, etc., that preserve the product will be crucial to a cost-effective
manufacturing strategy
Product in-Process Stability and Impurity Profiles
Stability
DOWNSTREAM PROCESS DESIGN METHODOLOGIES AND TOOLS

14.  Stability of the target molecule may also strongly affect its propensity toward certain types of interactions that can be
exploited in a purification process
Impurities and Contaminants
 The objective of purification is to either completely remove any quality deteriorating components from the drug
substance, or to reduce their content below acceptable levels from the patient safety perspective
 Product-related impurities and Process-related impurities are two major types of impurities
 Product-related impurities are molecular variants arising during manufacture and/or storage, which do not have
properties comparable to those of the desired product with respect to activity, efficacy, and safety
 Process-related impurities are chemical and biochemical bioprocessing reagents, inorganic salts, ligands,
solvents, and other leachables and extractables

15.  If, a process needs to be developed from scratch, then based on the product characteristics and types of
impurities, process data available from the product development activities, heuristic information, and literature
reviews a list of most promising technologies can be compiled and a few process sequence alternatives
proposed
 PD can be performed using established laboratory and pilot-scale scale-down models, and that scientific
principles employed will assure that results obtained and conclusions drawn from PD studies are representative
of the commercial manufacturing
 The evaluation of the effect of process variables one at a time, applying mathematical/mechanistic
modeling, use of the concept of the design of experiments, DoE
 Any combination of these methods can be applied in practice, depending on the level of complexity and
initial knowledge about the challenge at hand

17. Principle and guideline for of linear scale-up
Element Parameter
Maintain Bed height
Eluent velocity
Sample concentration
Gradient slope/bed volume
Increase Column diameter to reach the required column volume
Volumetric flow rate in proportion to column volume
Sample volume in proportion to column volume
Gradient volume in proportion to column volume
Check Reduction in wall support (increased pressure drop)
Sample distribution
Piping and system dead volumes

18. Process
modeling
• There are two basic modes
of process design that rely
either on static or on
dynamic models
• Static model: It is best
suited for process scale-up
and economy simulations
• Dynamic model: It is suited
better for capturing logistics
and manufacturing
variability
Different phases in process development and the general need
for modeling

19. Commercial Modeling Software
• SuperPro Designer
• BioSolve
• Bio-G
• aspenONE Pharmaceutical Solutions
• SIMBIOPHARMA

20. SuperPro Designer: Enables creation of the process flow diagrams and fairly user- friendly graphical
interface. Each unit operation (e.g., processing step) is editable. calculate appropriate size of the
equipment associated with the unit operation, including auxiliary equipment such as tanks, CIP skids,
etc.,
BioSolve: It is excel-based bioprocess modeling tool from Biopharm Services. In recent releases of the
software, multivariate
analysis and variability simulations using Excel add-in’s
Bio-G: It is a real-time modeling system. It is used from late-stage process development to large-scale
production. It make it possible to perform analysis on real-time data from the running process
aspenONE Pharmaceutical Solutions: It is an integrated life-cycle simulation tool that could be used from initial
design through plant start-up to operational support. The development of the model was performed in
incremental steps: gathering of
information, recipe details, backbone assembly, workarounds, model refinement, error checking, and
updates.
SIMBIOPHARMA: It is evaluate manufacturing from a cost, time, yield, resource allocations and risk
perspective.

22. Career Scope
Biological and
Agricultural
Engineers
Chemical
Engineers
Environmental
Engineers
Associate
scientist in
bioprocess
Research
associate
Quality control
engineer
Design
engineer
Manufacturing
engineer
Process control
engineer
Production
engineer
Technical
service
engineer

23. Biopharmaceutical
Industries

26. Salary package
DESIGNATION
SALARY PACKAGE
(APPROXIMATELY)
Trainee 3.25 – 4.50 LPA
Executive 5.00 – 6.00 LPA
Senior Executive 7.00 – 8.00 LPA

27. THANK YOU