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Industrial Platform Design forIndustrial Platform Design forProbiotic Production usingProbiotic Production using
Different BiofactoriesDifferent Biofactories
Prof. Dr. rer. Nat. Hesham A. El EnshasyChemical Engineering Pilot Plant (CEPP)
Faculty of Chemical and Natural Resources Engineering
University Technology Malaysia (UTM), Skudai, JohorE-mail: [email protected]
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Content
Probiotics (Science and Business)
Case Study: breast milk probiotics (novel infant formula)
Bioprocess manufacturing Platform Design
Proposed scaling up model for probiotics
Market and Future trends
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Probiotics =robiotics =Businessusiness
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The total market of Probiotics reached 6 US$ Billions by 2004
Most of Probioics business focused on Pharma, Food, Feed Industries
Global market for
Probiotics
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Lactobacillus strains Bifidobacteriums sp. Others
L. casei
L. rhamnosusL.acidophilusL. bulgaricusL. fermentumL. lactisL. johnsonii
L. reuteri
B. bifidumB. breveB. infantisB. lactisB. longum
S. boulardii
S. thermophilusE. faecium
Probiotics Business
Partners
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Ablility to survive in the extreme conditions of digestivetract
Adherence to epithelial cells and intestinal mucosa
Colonization potential in the human intestinal tract
Production of antimicrobial substances towardspathogens
Safety with regard to human use
Stability during storage under normal conditions
Probiotics Strain
Selection
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Inhibit pathogen attachment
Inhibit the action of microbial toxins
Stimulate immunoglobulin A
Trophic effects on intestinal mucosa
Saccharomyces boulardii
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Saccharomyces cerevisiae
Help to feed 6,3 Billion people
Save life for 150 million Diabetics
Produce drugs and vaccines for otherhundred thousands
EVERY DAY
Analysis of related
Process
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High Cell mass production
Adaptive strain to draughness and tolerate to moderate heat
Process Keywordsrocess Keywords
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Scaling up of the Process
Down Stream(Separation/Isolation/Purification and increase of product Stability)
Determination of process bottleneck(s)
Bioprocess Optimization in Lab. scale
(Development of cultivation strategy to reach the maximal productivity)
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Glucose repression
Oxygen limitation
MixingAeration
pH control
Foaming effect / Mixing
Determination of process bottleneck(s)Up-Stream
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0 5 10 15 20 25 30 35 40
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CDW[
gl-1]
Time [h]
Glucose[gl-1]
OD[%]
0.5 1.0 2.0
Fed batched batchcultivationultivationGlucose feeding rate [g l-1 h-1]
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&Mostly are Innovative proudcts with long R D phase
( - )Big difference in price between commercial and extra pure( , - )In Biopharmaceuticals product NO COMMERCIAL GRADES ONLY EXT PURE
Production under highly controlled sterile conditions with extra industrial( , , )Requirements depends on product type and safety cGMP HACCP ISO
The Product
The Process
The Business
( - )Long term Investment High Risk High Benifit Business
&Highly Competive mark based on Innovation and multi million US$ R D Cost
= ( )Time money
Main characteristics of Biotechnological Products
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Platforms in Biotech Industries
Product Based Platforms
Bioprocess Based Platforms
Biofactory Based Platforms
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Industrial Bioprocessing
Vaccine
Biopharmaceuticals
SolventsBakers yeast Organic acids Amino acids
AntibioticsEnzymes
biopolymers
rProteins MAb
SCP Biosurfactants
Probiotics
Plant Bioactivecompounds BioDiesel X
Pre
1940s
Pre
1980s
Post1980s
Biotechnological Products
Bio-insecticides
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Bacteria
Actinomycetes
Yeast
Algae
Plant cells
Insect cells
Invertebrate cells
Mammalian cells
Filamentous fungi
Biofactories in Biotech Industries
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Product Based and Cell Factory Based Platforms
Product Based Platform Cell Factory Based Platform
Less Flexible
Dedicated for one product(or branch of product)
Limited use as Toll-Manuf.
Less Expensive
For well-established products
Low-Value facility(in case of Sale)
More flexible
Can produce different typesof products from the same biofactory
(without or with minimal modifications)
Easily applied as Toll-Manuf.
More Expensive
For well-established products
and new products
High-value facility(in case of Sale)
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Current Bioprocess based Platforms
High Cell Density Cultivation Platform (unicellular MO)
Non-Newtonean fluid fermentation platform
1- rProtein Production (Bacteria/Yeast)(CEPP products / EntoGeneX Co. )
2- Cell mass production of novel probiotics (Bacteria/yeast)(CEPP products)
3- Non-rProtein production in Bacteria(CEPP products / EntoGeneX Co.)
4- Cell mass production of nitrogen fixing bacteria(All Cosmos Co.)
1- Polysaccharide production (Bacteria)(CEPP products)
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Current Biofactory based Platforms
Filamentous MO cultivation platform
1- Mushroom cultivation for bioactive metabolites production(CEPP products / Bioalpha Co.)
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CEPP platform will work as
Technology Transfer hub for Biotechnology companies
Technology developer from strain to tonnes of powder
CRO for local and International Companies
Incubator for Biotechnology based SME
Innovative Process Development for already marketedMolecules
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CEPP as Technology Transfer HUB
1- Technology transfer hub for biotechnology companies:
1.1. Phase I:- Cell banking- Technology Evaluation- Process re-adaptation- Dissolve of non-process related issues- Process scaling up and industrialization- Toll manufacturer to have short time market penetration
1.2. Phase II:- Consultation during the design and building new facility
(Basic Engineering, Project and process validation)- Human resource development and training of new staff
1.3. Phase III:- Master cell bank of the original strain- RTD centre for continuous process optimization
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Biofactorbased and Bioprocess based platformsand EDUCATION
Work as important component of the university educationsystem through teaching and practicing the platformmodels and the art of technology integration
Education tool for hand-on operation with industrial casestudy rather than teaching different subjects insegregated modes
Students (starting from undergraduate level) will work inindustrial climate structure. This will improve theirpracitcal skills and they will easily integrated in the
industrial society without lag time
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Biofactorbased and Bioprocess based platforms
and BUSINESS
Minimizing the risk of failure during technology transferprocess
RTD is the main assets of the BioTech based companies .This system supports the innovation based industry with
minimal direct investment
This provide the high skilled human resource required forBiotech Industries since students from undegrad. Levelwork in industrial projects and may hired by thecompanies doing this project
This type of platforms act as RTD hub and tollmanufacturing facility for SME (full acting incubator) tohelp companies for market penetration before largeinvestment in their own facility.
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Biofactorbased and Bioprocess based platforms
and SOCIETY
Increase the public awareness about Industrial biotech.production chain and future applications
Illustrate clearly this new technology to public throughvisits and public talks by experts to increase the publicawareness
Promote the culture of using biotech. based beneficialproducts as (Natural, Safe, Biofriendly) to the society.
This also help the companies to decrease the publicresistance against their new technology
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Microorganis (Type, thermo-adabtation, Draughness-adaptation)
Production facility (Up-stream) and control system
Product formulation (powder, micro-encapsulated, etc.....)
Cultivation mode / Scalability
Down stream requirements
Bioprocess design forioprocess design forProbiotic productionrobiotic production
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Thank YouThank You