kul bioprocess development.ppt

8/10/2019 Kul Bioprocess Development.ppt

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Bioprocess Development:An Interdisciplinary Challenge


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Back ground Recent advances in biotechnology and public concern

about environmental pollution and the sustainabilityof natural resources have rapidly transformed thenations many manufacturing industries, fromchemical to pharmaceutical, to become moreenvironmentally benign and bio-based.

For example, almost all major pharmaceutical

companies now dedicate more than 50% of their newdrug development to biotech R&D.

Likewise, large chemical companies, such as DuPontand Dow Chemicals, are aggressively developing new

bio-based products to replace petrochemical ones.


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HISTORY AND APPLICATIONS of BIOTECH

Biotechnology has beendescribed as the last greattechnological innovation ofthe twentieth century andhas touched upon almostevery aspect of human life,from healthcare to

agriculture to the productionof industrial products (Figure1).


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Historical milestones in the

development of biotechnology


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Some Major of Industrial Fermentation

Products


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Steps in Bioprocess

Development: Bioprocessing is an essential part of many

food, chemical and pharmaceutical industries.Bioprocess operations make use of microbial,

animal and plant cells and components ofcells such as enzymes to manufacturenewproducts and destroy harmful wastes.

bioprocesses have been developed for an

enormous range of commercial products,from relatively cheap materials such asindustrial alcohol and organic solvents, toexpensive specialty chemicals such asantibiotics, therapeutic proteins and vaccines.


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Our ability to harness the capabilities of cellsand enzymes has been closely related toadvancements in microbiology, biochemistry

and cell physiology Tools of modern biotechnology such as Rec-

DNA, gene probes, cell fusion and tissueculture offer new opportunities to develop

novel products or improve bioprocessingmethods.

Although new products and processes can beconceived and partially developed in thelaboratory, bringing modern biotechnologyto industrial fruition requires engineeringskills and know-how.


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The interdisciplinary nature of bioprocessing isevident

Look at the stages of bioprocess development requiredfor a complete industrial process.(see Fig. below)

These stages involve different types of scientificexpertise.

-(Steps 1-11) are concerned with genetic manipulation

of the host organism (molecular biology and

biochemistry).

Tools : Petri dishes, micropipettes, tubes, PCR machine,

microcentrifuges, nano-or microgram quantities of

restriction enzymes, and electrophoresis gels for DNA

and protein fractionation.;


9/25Figure1.Steps in development of a complete bioprocess for commercial new recProduct


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(Step13):Scale-up of the process starts. The first stagemay be a 1- or 2-Litre bench-top bioreactor equippedwith instruments for measuring and adjustingtemperature, pH, DO concentration, stirrer speed andother process variables.

Information collected: O2 requirements of the cells,their shear sensitivity, foaming characteristics andother parameters.

Limitations imposed by the reactor on activityof the organism must be identified. For example, if thebioreactor cannot provide O2 to an aerobicculturestarving or cell damage.

The situation is assessed using measured andcalculated parameters such as mass-transfercoefficients, mixing time, gas hold-up, rate of oxygenuptake,etc. It must also be decided whether the cultureis best operated as a batch, semi-batch or continuous

process;


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(Step 14): the system is scaled up again to apilot-scale bioreactor.

A vessel of capacity 100-1000 litres is built according tospecifications determined from the bench-scaleprototype.

The aim of pilot-scale studies is to examine theresponse of cells to scale-up.

Even though the geometry of the reactor, method ofaeration and mixing, impeller design and other featuresmay be similar in small and large fermenters, the effecton activity of cells can be great.

Loss of productivity following scale-up may or may notbe recovered; economic projections often need to bere-assessed as a result of pilot-scale findings.


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(Step 15). industrial-scale

If the scale-up step is completed successfully,design of the industrial-scale operation

commences. Particular attention is required to ensure the

fermentation can be carried out aseptically.When recombinant cells or pathogenic

organisms are involved, design of the processmust also reflect containment and safetyrequirements.


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(Step 16), Downstream processing

An important part of the total process is productrecovery, also known as downstream processing.

Product recovery is often difficult and expensive; forsome recombinant-DNA-derived products, purificationaccounts for 80-90% of the total processing cost.

Commercial procedures include filtration, centrifugationand flotation for separation of cells from the liquid,mechanical disruption of the cells if the product isintracellular, solvent extraction, chromatography,membrane filtration, adsorption, crystallisation and

drying. Usually First developed and tested using small-scale

apparatus Disposal of effluent after removal of the desired product

must also be considered.


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(Step 17).Packaging &marketing

After the product has been isolated in sufficientpurity it is packaged and marketed.

For new pharmaceuticals such as recombinanthuman growth hormone or insulin, preclinical and

clinical trials are required to test the efficacy of theproduct.

Only after these trials are carried out and the safetyof the product established, it can be released forgeneral health-care application.

Bioprocess engineers (or Pharmacyst) with adetailed knowledge of the production process areoften involved in documenting manufacturingprocedures for submission to regulatory

authorities (FDA or BPOM in Indonesia).


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As shown in this example, a broad range ofdisciplines is involved in bioprocessing.

Scientists working in this area are constantlyconfronted with biological, chemical, physical,engineering and sometimes medicalquestions.

It is important for Pharmacyst to keepexistence both in up stream and down streamprocess of bioprocessing.


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Description world market ofbiotech/fermentation product

EtOH

(x103

ton/year)

Citric acid

20010010

Glutamat

Penicillin derivat

Vitamin B12, B2

Vaccine, Therapeutic proteins

Protease, Amilase


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Table 1. Major products of biological processing


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A Quantitative Approach

The biological characteristics of cells and enzymes oftenimpose constraints on bioprocessing; therefore knowledge ofthem is an important prerequisite for rational bioprocess

(engineering) design. For instance :- thermostability the operating temperature of reactor?

- susceptibility of an organism to substrate determine

whether substrate is fed all at once or intermittently?

It is equally true, however,that biologists working inbiotechnology must consider the engineering aspects ofbioprocessing; selection or manipulation of organismsshould be carried out to achieve the best results in

production-scale operations.


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.

Another area requiring cooperation and understandingbetween engineers and laboratory scientists is mediumformation.

For example, addition of serum may be beneficial to growthof animal cells, but can significantly reduce product yieldsduring recovery operations

All areas of bioprocess development; the cell or enzyme

used, the culture conditions provided, the fermentation

equipment and product-recovery operations--areinterdependent. Because improvement in one area can bedisadvantageous to another, ideally, bioprocess

development should proceed using an integrated approach.


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kul bioprocess development.ppt

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