micro reactor technology is the industry ready for it yet

Microreactor technology: isthe industry ready for it yet?Microreactor technology (MRT) has recently been introduced to the pharmaceuticalmanufacturing circuit as a promising technology for the continuous processing of commercialquantities of Pharmaceuticals. Although MRT appears to offer many advantages compared withtraditional batch processing, it will require a change in thinking and practice if manufacturersare to accept it. we undertook a series of interviews with some experts to understand whattrue benefits MRT had to offer in the large scale manufacture of Pharmaceuticals and toascertain whether the industry is ready for it yet.

Fedra PavlouPharmaceutical

Technology Europe

T he FDA's Process Analytical Technology (PAT)Initiative^ was launched some years ago "to

support innovation and efficiency in pharmaceuticaldevelopment, manufacturing, and quality assurance",to "design and develop processes that canconsistently ensure a predefined quality at the end ofthe manufacturing process." sets of guidelines vi/erelaid out as part of the PAT framework, offering adviceto manufacturers on how to make their processesmore efficient. These included:

• Reduce production cycle times by using on-, in-,and/or at-line measurements and controls.

• Prevent rejects, scrap, and re-process ing.

• Real time release.• Increase automation to improve operator safety

and reduce human errors.• Improve energy and material use and increase

capacity• Facilitate continuous processing to improve

efficiency and manage variability; for example,by using dedicated small-scale equipment [toeliminate certain scale-up issues).

As part of the initiative, the FDA encouragetípharmaceutical manufacturers to abandontheir conservatism and to seek alternativesto traditional large vessel, batch processing

OCTOBER 2009 PHARMACEUTICAL TECHNOLOGY EUROPE

Microreactor technology

which, although responsible forthe successful production ofquality Pharmaceuticals, has itsdisadvantages. These disadvantagesinclude, the production of largequantities of unwanted byproducts,heavy use of energy resources,inefficiency, and excessive use ofstarting materials, such as solventsand catalysts.

Consequently, alternativesolutions were sought and attentionturned to a technology that wasonce only used in R&D laboratoriesand for small-scale production —microreactor technology (MRT).

MRT is based on continuousflow chemistry through reactorswith a typical height or widthof ' -1 mm, but with lengths of1 cm-1 m. Chemical reactions occurcontinuously through these tinymicrostructures to yieid thousandsof kilograms of product per hour,thus making the technologysuitable for large-scale, commercialproduction.

Although microreactors arethousands of times smaller thantheir traditional batch counterparts,they fundamental benefits, includingselectivity, reliability, rapid mixing,effective heat exchange, minimal

reagent and solvent volumes,speed, safety, easy process controland automation, simple scale-up,improved sustainability, reducedwaste, and cost-effectiveness.MRT also allows manufacturers toundertake certain, often hazardous,reactions that were not possible in abatch reactor.

Consistently under pressure toreduce costs, improve efficiency,reduce environmental damageand to remain competitive, and inline with the FDA's guidance, anincreasing number of pharmaceuticaland chemical manufacturers arelooking to the continuous, intensifiedmanufacturing processes offeredby MRT as a way to achieve some ofthese aims-

isthe pharma industryready for it?"The concept that MRT is suitablefor large-scale production has beenknown for some time, the problemhas been the availability of highquality, commercial equipment. Ibelieve the equipment that is nowbecoming available is making thelarge-scale applications develop,"says Paul Watts, Chief TechnologyOfficer at Chemtrix BV. Sergio

Pissavini, Business Director ofReactor Technologies at Corning,agrees: "Our company has decadesof experience in the chemicalindustry, but it was evident thatthe pharmaceutical industrywas becoming more and moreinterested in MRT for fine chemicaland pharmaceutical production.

"MRT has completely changed theway that industrial pharmaceuticalprocessing takes place; it requires ashift in methods and in thinking. It is forthis reason that we delayed introducingour MRT to the market. We needed themarket to be ready for it"Sergio Pissavini, PhD, Corning SAS

The focus, however, was no longeron small-scale production, but theindustry began to understand thebenefits that this technology hadto offer for high volume businessand industrial-scale production. Assuch, we too turned our attentionto pharmaceutical manufacture andconcentrated some of our technology

Sidebar 1: MRT in biotechnological applications

Erik Kakes. ir)ternat\or)al sales & MarketingDirector, Applikon Biotectinology BV

Micro bioreactor technology is used toperform high-throughput fermentationand celi culture. Because various researchprogrammes require that multiplemicro-organisms should be grown withhigh throughput under a variety of carefullycontrolled conditions, micro bioreactortechnology has been designed to offer thisenvironment, allowing many controlledreactions to take place on a single plate.The benefits of this technology can alsobe seen with recombinant clones, whichalso require culture under controlledconditions, at high levels of expression,high throughput and fast productionturnaround.

One key difference between MRT forpharmaceutical and biotech applicationsis sterility; with biotech applications, thesterility of the system is an extra hurdie.All manipulations and measurements must

be aseptic. This places extra demandsspecifically on the measurement andcontrol elements of micro bioreactors.

A real benefit, however, of microbioreactor technology is its contributionto greener methods; lower voiumesand single-use technology require lessresources and less energy per culture. Thisdirectly contributes to a greener approachto cultivation.

Recent innovations in the technologyinclude the use of fluorophor technologyfor noninvasive micro scale measurementof pH and dissolved oxygen; allowing largernumbers of cultures to run simultaneouslywith individual measurement and controlof important process parameters. Thisreduces the development time for newprocesses/products. Also, the amount ofmedium used is greatly reduced.

Although the majority of biotechnologycompanies have yet to be convinced bythe results obtained with the new microbioreactors, I do beiieve that the market

will grow. Once the industry recognizesthat the majority of processes parameterscan be easily transferred from smallvolumes to large-scale production usingthese systems, l predict it is a matterof time, several years perhaps, beforewe see widespread uptake. The leadingtarge biotechnology and pharmaceuticalcompanies have already embraced thistechnology, but the majority of smaller andmidsize companies will still have to follow.

We are investing in fed batch andcontinuous (perfusion) cultures, which,once available, we believe will furtherenhance the appeal of micro bioreactortechnology to industry.

Micro bioreactor technology allowsimproved consistency, data collectionand culture control thus allowing betterdecisions to be made sooner. Costs aresaved on identifying strains or moleculesthat would have later failed; this translatesinto overall cost savings and higherthroughput.

subscritje at www.pharmtech.com 23


investments on MRT for pilot rightthrough to commerciaUscalepharmaceutical production."

A large portion of pharmamanufacturers remain to beconvinced by MRT and its placein large-scale processing. Thisscepticism can, however, beprimarily attributed to the lack ofavailability of the technology; MRThas only very recently been madeavailable for the production of vastquantities of Pharmaceuticals, in fact,industry experts began to realisethe benefits of the technology inthis setting approximately 4 yearsago, making it a relative newcomerin the pharma manufacturing circuit.

"In a microreactor. we see less issueswith mixing and heat transfer, resultingin less byproducts. The reaction is onlylimited by the reaction kinetics, enablingbetter process control and a morereliable process"Andreas Weiler, PhD, SAFC

"MRT has compietely changed theway that industrial pharmaceuticalprocessing takes place; it requiresa shift in methods and in thinking.It is for this reason that we delayedintroducing our MRT to the market.We needed the market to be readyfor it," says Pissavini, Corningbegan commercializing its MRTless than 2 years ago and Pissaviniconfirms that European interestwas very strong to begin with,while the North American, Indianand Japanese marlcets are nowslowly following suit. Conversely,microbioreactor manufacturer,Applikon Biotechnology, has

witnessed a different geographicaltrend, "Our users in the US are moreopen to new technoiogies, whereasin Europe, the users want to test thesystems and see more proof thatit really works," admits Erik Kakes,International Sales & MarketingDirector at Applikon, Sidebar 1explains the benefits of MRT inbiotechnological applications,

"Perception relating to MRT andits use in full-scale manufacturinghas been quite negative, but i dothink that some of the technologieson the market in previous yearswere not ready to be used forcontinuous, large-scale processingand so perception has been informedby failed early-stage trials," admitsSophie Walton, Business Managerat the centre for Process innovation(CPl) UK. "I think there has alsobeen a lack of understanding of theskiil-set needed and the volumeof work required to fit complexchemical reactions to MRT to reallyreap the rewards. Quite oftenwe still see people trying to fitchemistry to these reactors withoutknowledge of the calorimetry orthe kinetics of the reaction, andfrequently we see customers whodon't really understand the reactionchemistry — usually because thechemistry has been run for so long inthe plant that they know what theyhave to do to achieve complianceon a batch without understandingwhy they do that in terms of thechemistry," she adds. According toWalton, a common misconceptionamongst manufacturers is that raisedreaction temperatures leads to moreside reactions and byproducts. "Weknow that in most cases this doesn'thappen because of the greatlyreduced residence time within thereactors," she explains.

Hampered by regulationsAny desire for new technology andinnovation in the pharmaceuticalindustry will, hov̂ rever, always beslightly dampened by regulations,compliance procedures and cost.Irrespective of whether a companybelieves in a new advance inpharmaceutical manufacturing ornot, the benefits need to be provenbeyond doubt before investments ofmoney and time can be made,

"The pharmaceutical landscapeis a highly regulated market withmany stakeholders, which makesit difficult and time-consumingto introduce a new productiontechnology," acknowledges AndreasWeiler, Global Business Directorat SAFC, "Although, when the topfine chemical companies started toexplore and market this technoiogy,the perception began to change," headds. This is evidenced by the manybig names in pharma that have openlyplaced their trust in MRT, includingSchering-Plough, sanofi aventis,Roche, GlaxoSmithKline, Novartis andAstraZeneca,

"Perception is gradually changing;we know of many large pharmaprojects currently underway in MRT,Many companies who do not haveprojects in this area are comingforward and speaking with CPl to seeif they can tap into the knowledgeand resource that we have, so theycan effectively 'catch up' with someof the companies that are way out infront in this form of pharmaceuticalmanufacturing," says Walton,

Advantages of MRTIt is clear that the pharmaceuticalindustry is beginning to understandthat there may be a place forthis exciting technology in theirmanufacturing facilities, but MRT

Sidebar 2: Selective nitration in a microreactor under cGMP conditions — A case study^

The companies DSM (fine chemicalmanufacturer) and corning (MRTmanufacturer).The brief to develop a process to performsafe, selective nitration, using pure nitricacid, under cGMP conditions in orderto produce quality product in industrialquantities.The challenge: The hazardous nature of

nitrations, particularly at commercial scale.The methods: A microreactor system wasdesigned that combined three key processsteps; nitration reaction, neutralization,work-up. An intensified process wasdeveloped that used the capabilitiesof Coming's reactor technology,which combined the advantages ofglass micro-structures with extraction

equipment. Scale-up risk was minimized byincreasing the number of reactor moduies,rather than increasing their size.The outcome Safe reaction under cGMPconditions; high chemical selectivityand low waste; predictable and reliableperformance; high quality end-product;short timeline; production of 25 metrictons of material on scale-up.


will not only require a change inthinking and processes; a significantinvestment of time and money willalso be necessary. Furthermore,not all reactions that are conductedin traditional large vessels can bedone in microreactors, although itis now thought that this relates to aminority of reactions. So why shouldpharmaceutical manufacturers takethe plunge?

flexible"One of the major benefits of MRTwhen compared with some othercontinuous technologies, such asthe spinning disk, is its flexibility. Forinstance, you can run many differentreactions on one reactor system,which was a common argumentpreviously held as a good justificationfor batch reactors," says Walton."Not oniy can you perform morethan one reaction in one system, butthere is less restriction on minimumfill volumes and you can ramp upyour manufacturing quantity easilyby scaling out the technology andadding units operating in parallel,"she adds. Pissavini agrees, confirmingthat a reactor can be customized fora specific reaction, thus customersdo not need to adept the chemistryfor the equipment. "Flexibility is areal advantage of MRT," he says. "Youcan first test a reaction in a smallstructure and then add several linesin parallel to your industrial process,thus you can very easily increase thevolume of your structure, yet you donot have the risk of loss of qualitythat you do if, for example, you wereincreasing a 200 L batch to a lOOO L."

According to Watts, one of the

most significant advantages of MRT isits ability to work on highly dangerousreactions, such as the nitrationreaction, recently reported by DSM(see Sidebar 2).̂ "The corning glassreactor enabled a hazardous reactionto be conducted safely under cGMPconditions. Other companies are nowdeveloping equipment with similarcapabilities," he explains, "i thinkthe recent validation to cGMP of theCorning reactor at DSM has addedconfidence to the market place,"confirms Walton.

Indeed, the successful productionof vast quantities of materialthrough industrial-scale operationof a hazardous nitration reactionusing MRT was something of aturning point for the technology andprovided strong evidence in supportof the technology's flexibility,efficiency and safety.

safe"The internal volume of themicroreactors is tiny compared withbatch reactors; hence reactionsthat are highly explosive on a largescale can be safely conducted incontinuous flow reactors becauseof the very good heat transfer. Anexample here is the synthesis ofnitroglycerine by Xian in China,"says watts, "The rapid dissipationof heat during a reaction conductedin a microreactor, coupled withthe low reactor hold-up time andreal-time in situ analytical evaluationof reactions, all add to the safety ofthese devices," he adds.

Improved efficiency, higheryields, greater reliability, less vi/aste;all descriptive of MRT processing

reáólioñs, wnen compared withthe traditionai, batch method. Itis, therefore, no surprise that thistechnology, although requiring aninitiai financial and time-intensiveinvestment, is undoubtedly viewed asthe more cost-effective option.

"The internal volume of themicroreactors is tiny compared withbatch reactors; hence reactions thatare highly explosive on a large scalecan be safely conducted in continuousflow reactors because of the very goodheat transfer"Paul Watts, PhD, Chemtrix BV

Reliable and efficient"In a microreactor, we see fewerissues vt/ith mixing and heat transfer,resulting in less byproducts. Thereaction is only limited by the reactionkinetics, enabling better processcontrol and a more reliable process,"says Weiler. "So some reactions thatmay take hours with batch processing,in fact take seconds or minuteswith continuous processing," addsPissavini. "With this increased control,you reduce the cost of quality control.With batch processing, our clients tellsus that three out of ten batches, onaverage, do not pass quality controland it may be that, out of thosethree batches, one will be wastedcompletely. You cannot predict theresult with batch processing untilyou receive the complete batch,"emphasizes Pissavini.



According to Watts, the vastmajority of scientific literature showsthat reactions conducted in MRT givethe desired product in higher yieldand higher purity compared withbatch reactions. "Meanwhile, thetime to development of new products'from scratch' is much shorter andclearly time savings means moneysavings," he remarks. "Once themanufacturing process has beendefined, you can move from the labright to commercial launch within 6months with MRT if a company sowished, with traditional technology,it could take 2 years to move theprocessing from the laboratory toindustrial scale. Time has a value inthe market," asserts Pissavini.

Walton agrees that the potential forcost reduction with MRT, because ofthe increased efficiency, decreaseddemand for energy, infrastructure,space and, in some instances, adecrease in the number of operatorsrequired for each shift, is a majorattraction. According to Walton,at CPl, they have witnessed manyinstances of improved yields, betterproduct conformity, fewer'batch'failures and an ability to handle somechemistries that carry significant

financiai risk in a batch. "There is alsoless leakage; with each reactor onlycontaining substance in the millilitrerange, you never really waste muchproduct," adds Pissavini.

Kind to the environmentThe pressure to reduce costs andincrease efficiency is permanentlyetched on the target list of allpharmaceutical manufacturersbut now, so too, is the pressure toreduce environmental impact. Fortoday's pharmaceutical manufacturerto remain competitive in a highlycompetitive market, they must seekto deveiop more intensified, safe, yetenvironmentally-friendly processes.

"MRT can definitely contribute togreener manufacturing," confirmsWalton. "Energy input is greatlyreduced as you are effectively heatinga narrow channel rather than a large,stirred tank that holds, for example,30000 L," she adds.

"Less byproducts also equalsless waste," says Weiler. "The greatheat transfer rate also allows somereactions to be performed withoutsolvents. Further, many processesthat are carried out in a batch reactormust be done at a temperature of

The author says...

Pharmaceutical manufacturers are constantly under pressure toincrease efficiency and reduce costs, whilst being kinder to theenvironment.Although batch processing for pharmaceutical manufacture yields goodquality product, this traditional process does have a number of inherentdisadvantages. For example; energy and time inefficiency, high volumesof solvent and reagent, large quantities of unwanted byproducts, andinconsistency of quality and mixing.Microreactor technology (MRT) has only recentiy been introduced tothe pharma industry for the continuous processing of commercialquantities of Pharmaceuticals.MRT is based on continuous processing through tiny reactor channelswith a typical diameter oí <i mm.MRT offers a number of distinct advantages over batch processing:selective, reliable, efficient, rapid mixing, effective heat exchange,minimal reagent and solvent volumes, speed, safety, control, lesswaste, environmentally-friendly, cost-effective.The number of reactions that can be conducted using MRT is increasing,whilst certain reactions that could not be conducted in large vesselbatch reactors, such as hazardous and potentially explosive reactions,can now be safely conducted with MRT.As more data is published highlighting the benefits of MRT in thecontinuous processing of Pharmaceuticals, and as the dynamics ofthe pharma market continue to change, widespread uptake of thetechnology will inevitably follow.

-70 "-C to control the reaction; similarreactions can be done at 0 "C or evenat room temperature m combinationwith shortened contact times, whichsaves a lot of energy," he adds.

In addition, it is very common inbatch reactions to require excesschemical reagents to complete areaction. "This is not frequentlyneeded in MRT and one canuse stoicliiometric quantities ofreagents. This clearly improves theenvironmental efficiency of theprocess," explains watts. "However,1 feel that one also needs to considerthe process as a whole; frequentlylarger volumes of solvent are usedin purifications than in the reactionsthemselves. If one can reducethe amount of waste in a reactionmixture, it simplifies the purificationoverall," he adds.

"There are massive healthand safety benefits too — as theinventory of chemical reacting ina microreactor channel at any onetime is so small when compared withtraditional systems and inventories,"explains Walton. She also highlightsthe energy and infrastructuresavings associated with MRTbecause of the small size of theequipment and the reduced amountof cleaning agents required.

Broad applicationsAlthough it is known that not allprocessing reactions that can beperformed in batch systems canalso be conducted in microreactors,the number of reactions that thisapplies to is lessening. "Years ago,only around 20-30% of reactionswould work with MRT. Today, webelieve that more than 60% couldbe accessible to this technology,"insists Pissavini. "We are currentlyperforming hydrogénation reactionson behalf of a customer with MRT,"he adds.

"In the past, continuous flowprocessing was mainly used forthe production of commodity,bulk chemicals, such as ethylene,styrene, ethylene oxide, monomers,and so on in metre-wide diameterchannels," says Weiler, He explainsthat it is now possible to performcomplex chemical reactions,particularly two-stage reactions, inan efficient manner inside these tiny

28 OCTOBER 2009 PHARMACEUTICAL TECHNOLOGY EUROPE


reactors because of the followinginnovations:• The change in tube diameter (from

several metres to 10 microns).• Different geometries can be used

in the mixing zones to support thedesired reaction.

• Different materials are used, suchas glass, stainless steel, hastelloy,which allow a broader variety ofchemical reactions.

"...if and when energy costs escalate tofuture projected levels, all companieswill be forced to make tough decisionson any inefficient existing assets andinfrastructure — again, MRT will be anobvious solution"Sophie Walton, Centre for Process innovation UK

Will all manufacturers adoptMRT soon?with all of the promise that thistechnology holds, is it a matterof time before all pharmaceuticalmanufacturers adopt MRT forcontinuous, large-scale processing?

"I don't beiieve so; there are manyinstances where a smaller scale,batch reactor will perform perfectlywell on a family of chemistries thata company may be performingand, in these instances, it makesno sense to change for the sake ofchange," says Walton. Weiler agrees,

"Whether a manufacturer opts toinstall MRT or not will depend onthe kind of reactions they have toconduct. Most of the classical, smallorganic API manufacturers will adoptthis technology for some of theirreactions. But it is important to noteMRT will not replace the classicalbatch approach; perhaps up to 10%of all reactions will be performedcontinuously," he predicts.

In contrast. Watts believes thatthe adoption of MRT by the majorityof pharmaceutical manufacturersis inevitable, "in reality, a lot isalready happening, but unfortunatelymembers of the industry do notalways publish what they are doing.From the published developmentsthat I have read, however, it is clearthat things are happening," he says.

"If researchers and universitiesbegin using this technology moreand start thinking of reactions ascontinuous processes, then wewill probably see a steady increaseover the next couple of years/'admits Weiler, "The pharmaceuticalmarket is highly confidential untildrug filing, so there rpight alreadybe Pharmaceuticals in the pipeline,created using promising continuousreactions that we just don't knowabout," he adds.

Walton agrees and confirms thatmany pharmaceutical companies areindeed undertaking research projectswith MRT, though confidentially (seeSidebar 3). "I do believe we will seea massive increase in the use of all

sorts of continuous reactors, MRT inparticular. As we require ever moreunusual molecules for our drugsand chemicals, our chemists aredesigning innovative pathways thatrequire precise process control andunderstanding, which will simply beimpossible in large batches. Here,without a doubt, MRT will have animportant role to play." Walton alsobelieves that the rising interest inpersonalized medicines, which willrequire smaller batch processing,will accelerate the uptake of MRT."Furthermore, if and when energycosts escalate to future projectedlevels, all companies will be forcedto make tough decisions on anyinefficient existing assets andinfrastructure — again, MRT will be anobvious solution," she explains.

Room for improvementAlthough MRT use in the large-scale, industrial processing ofPharmaceuticals is expected torise, research is still ongoing onthe improvement and refinementof this technology "Materials arecontinuously being improved; thechannel size and the geometry,for example," Weiier advises. "Thedevelopment of pulsation-freepumps is also an area where alot of investment is being made.Hopefully we will also see moreuser-friendly and cheaper kits, suchas all-in-one solutions with MR,pumps and temperature controldevices, including training platforms.

Sidebar 3: How Centre for Process Innovation (CPl) UK partners with industry to promote MRT

Sophie Walton. Business Manager at CPl UK

we have partnered with Corning on itsAdvanced Flow Reactor Technologyto demonstrate the value of MRT topharmaceutical clients who can work withus to trial the technology at minimum risk.The facility is relatively new to CPl, havingonly opened for commissioning projectsin August 2008, since then we have beenworking on several large projects for top10 pharma clients. These projects usuallytake the form of a "look and see" feasibilityproject on the target chemistry, whichgenerally lasts two weeks and is relativelylow cost and low risk for the client. Fromthis we can achieve over 50 data points

under different reaction conditions andit gives us a real feel for any significantbenefit of the flow reactor on thechemistry We usually then run into a moredetailed "optimization phase" which reallyproves the concept to the client.

we have been working on criticalprojects for these customers sounfortunately they have all been highlyconfidential to date. However, we hope,in the next 6 months, to collaborate withsome of these clients on separate projects,specifically to create pubiishable resultsand case studies, we will then also be ableto publish the names of the high profilecompanies involved, so watch this space!

In addition, we have collaborated

with some smaller companies, whichwe can talk about. For example, we aredue to kick off a project with innovativeUK-based SME LyraChem, which aims tojointly develop groundbreaking chemicalreactions, and then upscale these usingMRT. The first project to come through islikely to be a direct amidatiôn method forpharmaceutical production, which haspreviously been considered impossible toperform and is a step change in reactionchemistry.

To read more about hovw CPl works withindustry to promote innovation, please goto www.pharmtech.com/cpi

30 OCTOBER 2009 PHARMACEUTICAL TECHNOLOGY EUROPE


Currently, a lot of MRT knowledgeis covered by confidentialityand it IS not easy for studentsor researchers to be trained inthe technoiogy," admits Weiler.According to watts, modificationssuch as downstream separation,in-line anaiyticai inspection forquality control, and full integrationinto one continuous process willenhance the attractiveness of MRT topharmaceutical manufacturers.

Overall, Weiler believes that, ifresearchers and engineers start tothink of processes as 'continuous'processes at the early stages of thepharmaceutical process, this willclearly improve the time-to-marketfor new products. "We will seeimproved selectivity and morereliability leading to less negativescale-up effects," he says.

"Industry is already making a goodstart in trialling MRT; however, wewould like to see a greater successrate in these trials, as we haveheard rumours within industry ofsome disappointing results withcontinuous processing, which wethink could have been avoided hadthe right approach been taken,"comments Walton. She advisesthat companies must use the rightsupport from contractors and reactormanufacturers when trialling the newtechnology, "this is the key to successin many instances," she explains. Shealso insists that companies shouldnot expect to have all the right skillsin-house. "Quite often, collaboratingwith companies with a proventrack record of implementationincreases the success rate greatly,we know that in industries suchas the pharmaceutical industry,collaboration on cutting-edgechemistry can be hard for theintellectual property owner to cometo terms with. But we beiieve it reallyis the key to success, so long as thecorrect partners are selected for thecollaboration." she emphasizes.

in summaryMRT offers pharmaceuticalmanufacturers clear benefits.Continuous processing is associatedwith a number of advantagescompared with traditional batchreactions, including enhanced safety,efficiency, cost-effectiveness, waste

and reagent-use minimization,greater speed-to-market, to name buta few. However, with the benefits ofthe technology in a pharmaceuticalsetting only recently being realized,it wili be some time before usebecomes more widespread. Andalthough MRT will never fully replacebatch processing for large-scalemanufacturing, the clear benefits andthe expanded number of reactionsthat can occur with the technologycertainly make it appealing.

As companies continue to feel thepressure to reduce costs, increaseefficiency, alter infrastructure, andincrease their portfolio, whilst beingkind to the environment, we expectMRT to appear on the radars of mostcommercial-scale pharmaceuticalmanufacturers. As more data becomeavailable, demonstrating the benefitsof this exciting technology in themanufacture of Pharmaceuticals,and as the dynamics of thepharmaceutical market continueto change, veering towards morecomplex molecules and personalizedmedicine, the widespread adoption ofMRT will be inevitable.

"The future lies in all processesbeing physically connected,"concludes Pissavini.

References1. FDA Guidance for Industry:

PAT — A Frameworlc for innovative

Pharmaceutical Development,

Manufacturing, and Quality Assurance

(September 2004).

www.fda.gov

2. s. Braune ei al.. Chemistry Today, 27(1),

1-4 (2009).

ContributorsSergio Pissavini, PhDis Business Director ReactorTechnologies at Corning SAS, [email protected]

Erik Kakesis International Sales a MarketingDirector, Applikon Biotechnology BV,The [email protected]

Sophie Waltonis Business Manager at the centre forProcess innovation in the UK.Sophie.walton@u)c-cpi.com

Paul watts, PhDis Chief Technology Officer atChemtrix BV, The [email protected]

Andreas Weiler, PhDis Global Business Director at SAFC,[email protected]

Fedra Pavlou

is Editor-in-Ciiief of PharmaceuticalTechnology Europe.


micro reactor technology is the industry ready for it yet

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