ICBWI 3rd. Presentation

8/8/2019 ICBWI 3rd. Presentation

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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]
mailto:[email protected]:[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

Documents

ICBWI 3rd. Presentation