The Basics of Bioprocessing

quality Technology Netw • WHAT IS SIOPROCESSING USED f OR? The pharmaceutical industry uses bioprocessing to produce a variety of products, such as therapeutic proteins, vaccines and. antibiotics (e.g., pen icillin}. But it's ulso used ilcross other sectors to crcilte other valuublc products. For cxilntplc, it ciln be used to produce biofucls front plilnts and ulgue. recHNiOUeS BiOPROCeSSiNG &IOPROCESSING ORGANISMS A variety of different organisms are used in bioprocessing accord.ing to their characteristics: MAMMALIAN CELLS &ACTEl?I PLANT CELLS (£SCHE!i'ICHIA C Slo-1111 grovvth rate Fast growth rate VeflJ low cost o High growth rate • o • High cost Mcdiurn cost High yield Low·cost • • • • Mediurn -high yield High yield Lovv contamination high yield • Medium yield • risk s High contamjnation risk Lo,,v conlan,ination • 1'1ediurn risk High product quality contamination risk k High product quality • High product quality • Mediurn product Very high sea.le-up Low product quality • Low scale-up capacity capacity a High scale-up High scale-up capacity Cilpilci Organisrns arc cultured in systcn1s called. biorcactors or fcrmcntcrs. They provide cl controlled cnvironntcnt for cells to grovv ilnd rnultiply. Biorcilctors ilnd fcrrncntcrs arc csscntiully the silrnc - scientists cultivating bucteriil, yeast or fungi typically refer to these syslems as fermenters, and the term bioreactor is cornmonl used for n,a.mma.lian cells. m SYSTeMS BIOPROCeSSING The most frequently used biorcc1ctor •with a sirnple design and lo- operating costs. Irnpcllcrs, connected to cl motor, STIRReD-TANK are used to agilale the culture and aid heal transfer. BIOReACTOR They arc highly flexible and arc available in different volumes, heights and diameters for different types of cultures. •o An alternative to rnechanically (j\ O O (j\ o An alternative to rnechanicall Q ( ( o O O agitated systems, airlift reaclors o• f..L:;1,;J 0 0 R'lfr 0 0 t• t • are rnore suited for cells sensitive - 0 AIRLIFT ,, 00 0 ,, 00 0 - 0 0 ,; 0 0 ,), 0 t• are rnore suited for cells sensitive ·:' ,.: ...., •:: 0 to heat and shear stress. ,. 0 ::raft 0 O I. " C 0 lut:,: C . ,; 0 0 ), ,.: " . 0 ,; 0 ·: 0 0 ,, 00 0 - 0 0 ,; 0 0 ,), 0 t• are rnore suited for cells sensitive ·:' ,.: ...., •:: 0 .. ::raft 0 to heat and shear stress. 0 0 O C 0 " lut:,: C 0 C .0 0 C " 0 0 0 o• o Hi BIOReACTOR o• • 0 a· • • • 0 1 They agitate the cullure by i o.• bubbling gas to stir cells iln nutrients. Air Ai. Air AND -BATCH FeD BATCH BIOPROCeSSING CONTINUOUS There are three rnajor lypes of culluring with the com1nonly used stirred-tank reactors: batch, fed-batch and continuous. Batch is a one-time process, fed-batch uses controlled nutrient additions and continuous culturing majntains a steady state vvithout interruption 1 . :.;,,nll",·riS,\ n.o.-·,::: o,,, . SATCH F£D-&ATCH CONTI NUOUS All ingredients arc uddcd to This cxpunds upon batch Mcdiil and nutrients arc the ferrnenter at the ferruentation by adding continuously added, while beginning of the process. a.ddiliona.l rnedia. and old n,edia is removed to nutrients to boost growlh allow fermentation to It is a closed system. It and product yield. This is a. continue without reaches c01npletion \111h semi-closed system. interruption. nutrients are depleted, products accurnulate and This irnproves effi.ci.ency This is an open systern. growth hcls slowed. and ullows rnorc control. This is easy to set up, but nol the rnosl efficient process. DOwNSTReAM AND UPSTReAM PROCeSSING The bioprocessing workflow is broadly separated into upstrearn and downstrean1 processing, though their definitions a.re not universally agreed-upon. Here is a simplified bioprocessing vvorkfl.o UPSTREAM HARVEST DOWNSTREAM Mcdi. C:tllcultur r Filtrillio f Separat1on PurifiC<lllOn Fink;hing Uulk slorugc filling ] Rarves hydrallon b1orta.cto collection I I Formulation and hydration Cell l'.'.U Harvest Sieparauon ,md pur1fic.a1ion final idl and Uni.sh 1 WHAT IS UPSTREAM PROC£SSING? WHAT DOWNSTREAM PROCESSING? rs The initial phase of bioprocessing, from The isolation and puriticati.on of the engineering bacterial/mammalian cell resulting biosynthetic product lines through to expansion of the culture Examples: ilnd hr1rvesting Product capture Examples: Filtratio Cell line de •v eloprnen • Sterili •z ation Purification • Forrnulclting fcrrncntation rncdii Polishing cbNSIDeRATIONS KeY · APPLICATIONS Bi0PR0CeSSING SIOFUELS SIOPHARMACEU TICALS CELL AND GENE THERAPIES Biofucls ilrc rcncwublc Also known as biologicil Cell therclpics use rc fuels made from biornass. products or biologics. engineered cells to rcslore They a.re a.n alternative to biopharmaceuticals a.re or in,prove cellular fossil fuels as they are more manufactured frorn living funclions - such as sustainable and produce organisms. cancer immunotherapies fewer greenhouse oases. - ,,vhile gene therapies These can include modify genes in target To produce biofuels, therapeutic proteins, cells to prevent or treat rnicroorgunisrns r1rc used antibodies and vaccines. genetic diseclses to ferment suaars front str1rch-contilining crops - such as sugarcane - to produce elha.nol and carbon dioxide. CHALLeNGeS BIOPROCeSSING TReNDS FUTURe g CHALLENGES: FllTURE TRENDS: Fl • 1''1i1intr1ining consistency when trilnsitioning • Increased interest in continuous r front lub-scalc to industriill-scale production, processing to reduce costs and increclsc as well as maintaining good manufacturing productivity and quality. practice (GlvJ:P) during sea.le up. • Implementing automation may reduce • Maintaining quality and avoiding hands-on time and human error and contam jnation increase reproducibility whi.le preventing cilpilcity constraints. • Hiring <1nd retaining cxpc1ienced production stuff, espcciully ·,vith continued grovvth in the demund for bioproccssing. • Ensuring large-scale production remains sustainable and environmentally friendly, especially vvith the grovvth of single-use devices instead of stainless steel. Sponsored by: THe BA S IC S OF •