2
Journal of Biotechnolo gy 131S (2007) S188–S195 Industrial Biotechnology INNOVATIVE DOWNSTREAM PROCESSING 1. Eva luating bio pharmaceu tic al eco nomics and cap aci ty wit h process modelling and simulation tools Victor Papavasileiou a,, Demetri Petrides b a  Intelligen Europe, Leiden, Netherlands b  Intelligen, Inc., 2326 Morse Avenue, Scotch Plains, 07076 NJ, United States The capit al investment for new biopharma ceuti cal manuf ac- turing facilities is around D 4000L 1 of bioreactor capacity. Moderate to large facilities can cost hundreds of millions of Eur os, yet suc h in ve stments are often made with unc ert ain inf or - mation about process performance, media and materials prices, and market conditions. This paper presents a systematic way to evaluate the critical costs and capacity issues in biophar- maceutical plants. Examples will be presented on determining the target product titre, optimising bioreactor batch size and cho osi ng whe re or whethe r to use dis pos abl e (si ngl e-u se) equ ip- ment. Since many process decisions must be based on partial or uncertain information, this presentation will also describe how to evaluate the risk associated with process and economic assumptions. doi:10.1016/j.jbiotec.2007.07.333 2. Biotechnological process for chitin recovery out of shrimp waste Gabriele Daum a , Helen St ¨ ober a , Kerstin Veltrup b , Friedhelm Meinhardt b , Bernward Bisping a,a University of Hamburg, Department of Chemistry, Division of Food Microbiology/Hygiene, Biocenter Klein Flottbek, Ohn- horststr . 18, 22609 Hambur g, Germany b Westfaelische Wilhelms-Universitae t Muenster , Institut fuer  Molekulare Mikrobiolo gie und Biotechnologie , Correns str . 3, 48149 Muenster , Germany Chitin (poly -(1 4)-  N -acetyl-d-gluc osami ne), a polys accha - ride which is common in the carapace of insects and crustacea, is needed as precursor for chitosan. Chitin, in particular its deac etyla ted derivative chito san, has numer ous appli cations, such as in pharmaceu tical products , cosme tics, dairy prod- ucts, in waste water treatment, agriculture and biotechnological products. Routinely applications require specic structures, and ef fecti ve nes s of polymers wasshown to dep end on themolecula r weight and the degree of acetylation (Muzzarelli et al., 1986). Exo sce letonsof crustaceansarethe ke y sou rceof chi tin . Lim- itations of utilization are high costs for purication done by chemical processes, which include alternating acid and alkali treatments, resulting in large amounts of liquid waste of harsh chemicals. A biotechnological reconditioning of shrimp shell waste rep- res ents an alt ern ati ve . Suc h process inc lud es dep rotein iza tio n of shrimp waste and removal of calcium carbonate ( Healy et al., 1994). Since the app lic ati on of enz yme s, tho ugh ef fec ti ve ly use d in laboratory scale (Gagne and Simpson, 1993), causes uneco- nomical pro ductio n cos ts, the use of li vin g mic rob es, fac ili tat ing efcient chitin purication, is desirable. For demineralization of shrimp shells a fermentation with lactic acid bacteria was performed. Using 25% (w/v) waste, up to 95% of mineral salts were removed. In a further fermentation proteins were hydrolyzed by Bacil- lus licheniformis. A chitinase-decient strain was isolated from Indonesian shrimp waste and microscopically and physiologi- cally determined. Molecular characterization was performed by sequencing the 16S rRNA gene. Genetic work for enhancing protease production was suc- cessfully performed. References Gagne, N., Simpson, B.K., 1993. Food Biotechnol. 7, 253–263. Healy, M., Romo, R., Bustos, R., 1994. Resour. Conserv. Recycl. 11, 139–147. Muzzarelli, R.A.A., Tanfani, F., Emanuelli, M., Chiurazzi, E., Piani, M., 1986. In: Muzzarelli, R.A.A., Jeuniaux, C., Gooday, G.W. (Eds.), Chitin in Nature and Technology. Plenum Press, New York, p. 469. doi:10.1016/j.jbiotec.2007.07.334 0168-1656/$ – see front matter doi:10.1016/j.jbiotec.2007.07.332

La optimización de la recuperación de quitina de crustáceos desechos

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Journal of Biotechnology 131S (2007) S188–S195

Industrial Biotechnology

INNOVATIVE DOWNSTREAM PROCESSING

1.

Evaluating biopharmaceutical economics and capacity with

process modelling and simulation tools

Victor Papavasileiou a,∗, Demetri Petrides b

a  Intelligen Europe, Leiden, Netherlandsb Intelligen, Inc., 2326 Morse Avenue, Scotch Plains, 07076 NJ,

United States

The capital investment for new biopharmaceutical manufac-

turing facilities is around D 4000L−1 of bioreactor capacity.

Moderate to large facilities can cost hundreds of millions of 

Euros, yet such investments are often made with uncertain infor-

mation about process performance, media and materials prices,

and market conditions. This paper presents a systematic way

to evaluate the critical costs and capacity issues in biophar-

maceutical plants. Examples will be presented on determining

the target product titre, optimising bioreactor batch size and

choosing where or whether to use disposable (single-use) equip-ment. Since many process decisions must be based on partial

or uncertain information, this presentation will also describe

how to evaluate the risk associated with process and economic

assumptions.

doi:10.1016/j.jbiotec.2007.07.333

2.

Biotechnological process for chitin recovery out of shrimp

waste

Gabriele Daum a, Helen Stober a, Kerstin Veltrup b, Friedhelm

Meinhardt b, Bernward Bisping a,∗

a University of Hamburg, Department of Chemistry, Division

of Food Microbiology/Hygiene, Biocenter Klein Flottbek, Ohn-

horststr. 18, 22609 Hamburg, Germanyb Westfaelische Wilhelms-Universitaet Muenster, Institut fuer 

 Molekulare Mikrobiologie und Biotechnologie, Corrensstr. 3,

48149 Muenster, Germany

Chitin (poly␤-(1→ 4)- N -acetyl-d-glucosamine), a polysaccha-

ride which is common in the carapace of insects and crustacea,

is needed as precursor for chitosan. Chitin, in particular its

deacetylated derivative chitosan, has numerous applications,

such as in pharmaceutical products, cosmetics, dairy prod-

ucts, in waste water treatment, agriculture and biotechnological

products. Routinely applications require specific structures, and

effectiveness of polymers wasshown to depend on themolecular

weight and the degree of acetylation (Muzzarelli et al., 1986).Exosceletonsof crustaceans arethe key sourceof chitin. Lim-

itations of utilization are high costs for purification done by

chemical processes, which include alternating acid and alkali

treatments, resulting in large amounts of liquid waste of harsh

chemicals.

A biotechnological reconditioning of shrimp shell waste rep-

resents an alternative. Such process includes deproteinization of 

shrimp waste and removal of calcium carbonate (Healy et al.,

1994). Since the application of enzymes, though effectively used

in laboratory scale (Gagne and Simpson, 1993), causes uneco-

nomical production costs, the use of living microbes, facilitating

efficient chitin purification, is desirable.

For demineralization of shrimp shells a fermentation withlactic acid bacteria was performed. Using 25% (w/v) waste, up

to 95% of mineral salts were removed.

In a further fermentation proteins were hydrolyzed by Bacil-

lus licheniformis. A chitinase-deficient strain was isolated from

Indonesian shrimp waste and microscopically and physiologi-

cally determined. Molecular characterization was performed by

sequencing the 16S rRNA gene.

Genetic work for enhancing protease production was suc-

cessfully performed.

References

Gagne, N., Simpson, B.K., 1993. Food Biotechnol. 7, 253–263.

Healy, M., Romo, R., Bustos, R., 1994. Resour. Conserv. Recycl. 11, 139–147.

Muzzarelli, R.A.A., Tanfani, F., Emanuelli, M., Chiurazzi, E., Piani, M., 1986.

In: Muzzarelli, R.A.A., Jeuniaux, C., Gooday, G.W. (Eds.), Chitin in Nature

and Technology. Plenum Press, New York, p. 469.

doi:10.1016/j.jbiotec.2007.07.334

0168-1656/$ – see front matter

doi:10.1016/j.jbiotec.2007.07.332