Tài liệu les biotechnologies au service de la durabilite industrielle doc

Its the logical extension of the Task Forces previous activities, which culminated in a maior report, Biotechnology fr Clean Indostal Products and Proves which appeared in 1998, This pub

The Application

of Biotechnology

to Industrial Sustainability

The Application

of Biotechnology

to Industrial Sustainability

SUSTAINABLE DEVELOPMENT

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ORGANISATION FOR ECONOMIC CO-OPERATION ‘AND DEVELOPMENT Pursuant to Article ofthe Convention signed in Pads on Lith December 1960, and which came into foyce on 30th September 196, the Organisation for Economlc Co-operation and Development {OECD} shall promote policies designed:

= to achieve the highest sustainable economic growth and employment and a ssing standard of living in Member counties, while maintaining financial stability, and thus to contibute to the development ofthe world economy:

~ to contibute to sound economic expansion In Member as well as non-member counties In the process of economic development and

= to contribute to the expansion of world trade on a mult accordance with international obligations

“The otiginal Member countries of the OECD are Austia, Belgium, Canada, Denmatk, France, Germany, Greece, Iceland, ireland, italy, Luxembourg, the Netherlands, Norway, Portugal, Spa, Sweden, Swiverland, Turkey, the United Kingdom and the United States, The following counties became Members subsequently through accession at the dates Indicated hereater Japan (25th April 194), Finland (28th January 1969), Australia (7th June 1971}, New Zealand (29th May 1973) Mexico (18th May 190, the Czech Republic 2Ist December 1995), Hungary (7th May 1996), Poland (22nd Novernber 19%), Korea 12th December 1996) and the Slovak Republic (14th December 2000) The Commission ofthe European Communities takes part inthe work ofthe OECD (Atile 13 of the OECD Convention,

eral, non-discriminatory basis

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FOREWORD

‘Ata meeting in Berlin on 30 May 2000, the Task Force on Biotechnology for Sustainable Industial Development of the OECD's Working Party on Biotechnology (WDB) was commissioned to prepare a study which has resulted in the present publication Its the logical extension of the Task Forces previous activities, which culminated in a maior report, Biotechnology fr Clean Indostal Products and Proves which appeared in 1998,

This publication brings together a wide range of case studies in order to show how companies have implemented biotechnological processes and the means they have wsed to assess benelits in terms of cost and sustainability The case studies were analysed to extract key messages and, to make comparisons easier, they ae presented in as uniform a format as possible The report Is intended for two key constituencies, senior managers in industry and government policy makers

As industial managers become more aware of what thelr colleagues have achieved, they may be encouraged to explore the possibilities of biotechnology; goverment policy makers may use the report a8 a basis for policy guidelines or for national programmes to underpin the expansion ol industrial biotechnology

This volume was prepared by Dr Mike Gifiths (OECD consultant, whose efforts on behalf of the Task Force are greatly appreciated, He worked in close collaboration with an editorial team comprising

Dr Anders Gram (Novorymes 4/5, Denmark Dr Witrud Treflenfeldt (Dow, Germany) Dr Ut Lange (GMBF, Germany); Dr Tery Meintyre (Environment Canada, Canada); Mt Oliver Wolf (European Commission/JRC/IPTS, Spain), OECD support was provided by Ds Salomon Wald (Head of Biotechnology Unit) and Dr Yoshiyasu Yabusakl ofthe OECD Directorate for Science, Technology and Industy

The OECD wishes to express its thanks to all Task Force participants (see Annex 1) and, in particular to the chair, Dr.John Jaworski (Industry Canada, Canada); and the vice-chais, Dr Brent Erickson (810, United States), Dr Ryuchiro Kurane (Kubota Co Lid Japan), Dr Joachim Vetter IBMBF Germany) and Me Olver Wolf European Commission IRCAPTS, Spal

Thanks also goto all those who gave their assistance and time during the preparation of the Individual case studies: Ox, Udo Koller IHotfmann Li-Roche, Germany), Dr Burghard Kenig Biochemie, Germany}, Prof Alle Bruggink (DSM, Netherlands), Dr Satoru TakamatSu (Tanabe Selyaku, Japan)

Dr Robert Holt {Avecia, United Kingdom); Dr Kanehiko Enomoto (Mitsubishi Rayon Japan);

Dr Jonathan Hughes (iba Specialty Chemicals United Kingdom) Dr Falmai Binns (Bavenden, United kingdom}; Dr David Glassner (Dow Carll, United States); Mr Oliver Wolf |RC/ECIPTS, Spain),

Dr Cees Buisman [Paques, Netherlands}; Dr Dieter Sell (Dechema, Germany); Dr Azim Shari (Doma Canada), De Terry Meintyee (Environment Canada, Canadal Dr jun Sugiura (Oji Paper, Japan,

Dr Dave Dew (Billiton, South Alea, Mr Jef Passmore (logen, Canadal, Mr Dave Knox (Ml, United kingdom) and Dr Allan Taynam (BP Exploration, United Kingdom), The OECD gratelully acknowledges the financial support provided by Canada, Germany, lapan, the United Kingdom and the European Commission for this work

The report is published on the responsibility ofthe Secretary-General of the OECD and does not necessarily rellect the views of the OECD or its Member countries In addition, it must be emphasised thatthe mention of industrial companies, trade names or specific commercial products or processes does not constitute an endorsement or ecommendation by the OECD,

TABLE OF CONTENTS Execute Summary `

Analysis and data gathering by compas

Becton making pd denon makers

hair Key Issues and Conclusions

‘Technica eiutes ofthe alienate processes Aevantages and iesdvatasce

Description athe innovation proces

Summary and conlsions

os stip 3 Blotechaologleal Production ofthe Anite C

‘Techeical descpice

sternal and eral nlicing facto

Summary and conclsions

halesin (OSM, Netherlands)

3

case sti 5 Manufacture of S-chloroproplone Acid (Avec, United Kingdom)

‘Techni description of procese

Advantages Histon ofthe novation proces and dandvantager

Summary and conclusions

{ise Sti 6 Emgnadk Production of Acrylamide (Msubishl Rayo

Suvmary and conclusions

Cu Sty 8 Ennyme-Catalaed Synthesis of Polyesters(Baxenden, United Kingdom)

Exynuranertl bens hod dispel options

Lie yee Inventory of PLA polymers

‘ase st 10, A Vegetable Ol Dogumming Enzyme (Corel, Germany

Intodvcton

Technical fates ofthe ney Max process

‘Advantages othe EnzyMox proces Deseription othe process of novation

Strmmary and conlsions

(Cue Study 11 Water Recovery na Vegetable-processing Company (Pastost, Netherland)

“echnieafeatares Deerption othe insaiaion

Suimary and conclusions

os std 12, Removal of Bleach Residues In Texte Flnchng (Win

¬

TeênoledizcrsUie pecc= Desaription a analysis

Reaale

Summary and concisions

es stip 13 Emzymatle Pulp Bleaching Process (Leykam, Aust}

Ineeedueien,

‘The innovation goal bicpuiping

‘The biopulping method

‘The innovation proces Favoursbie and untwourable factors

Cae Std 14 Une of yl

Inceduction

Enfiennenni aves

Pulping ana bleaching

Pressures for change

Summary and cnclsions

Amer A statu of Fulping Enzymes

‘ame 8 logon’ Xylanase Business

es Std 15 Life Cycle Assessment om Enryme Bleaching of Wood Pu

Objective be suấy

Results and đaonsden

omparson of eneymebizaching and ECF bleaching process

Eonchsions

Cau Stdy 16 O-xte Prodecdon of Kylanace (Of Paper Japan)

Expetience with the enajme production operation Cont bereits

Summary and concisions

cee Std 17 A Gypsumtee Zine

Introduction

Pece docipier

Spettional expends

Environmental impact

au Stdy 18 Copper Bleaching Technology (Bilton, South Afric)

‘sal enue Desctpton of the process of innovation

Process selection Smmary and cncisions

Cee Stdy 19, Renewable Feels~

‘ase sti 21, Use of Emymos In Olt well Completion (1, BP Exploration, Unltd Kingdom) bs Intodvcton Tan mg, Hà Hà Blotechoaogil proces Hà

‘Advantages and disadvantages 16

st of Boxes 1, The leo stemative technologies 2

2 Etsmples of prosranmes and intitives i

4, Shellr approach fo surtanable development 6

4 Lysine eedaddtive 2

5 Techniques for process analysis ke

8 Lie ele analysis a bain manulacare »

8 Waterreceulation nthe paper industry 6 Apaper mil ase study %

1 Casesby sector and county "

2 Comparative fl eel CO; emissions B

5 Coatond environmental benetis Wom cases „

4 Led et chemical and biological pmenies m

4, Relative cont of batch and continuous Worldwide acrylamide production capaci processing ot an

0 Development ot new enzymes B

11 Comparison of eneayconsumetion „

12, Comparizon of €0s production ” 1S, Comparson of waste production and weatnent ”

TẢ Relative consumption of aw mater and erica By 13: Consummation hgter ond cut conventional andl cnnaic ining 2

16 Groundwater quay ard guidelines fo drinking water quality „

Ir, Relate advantages of diferent water sources

lẽ Typeal water quang da mi

20 Total numberof Bleaching processes wth the Kapparym che wor

21, atoll load i! per machine type sn vit of ne H

21 Souings acordingto type of mechine tà

2, Savings fenery water anime withthe enayme process ta

2 Comparcon of processes by environmental impact category nr

26, Theratng of emissions by esoure consumption his

27, Properties ol we sjlanses Hà

28, Emesone reduction ad est license "

st of Figures

5 Enayme production operation là

5 Comparison af erating cost for smetting and bioleaching ho

6 Primary eoppe production by process route he

4 Qualtave tanking nN

5 Comparison athe total eneray demand orth production fwadiianal peel and E0 ful diferent

© Comparzon af reenbouse gae missions inaiferetscennos rom the whole ie cycle o traditional petal and E10 fel no

EXECUTIVE SUMMARY Background

In 1998, the OECD published Bitchincloy jor Clean Industral Products aed Presses That volume set out

‘many of the challenges for developing techniques to measure environmental friendliness and highlighted the potential contibution of various management tools However, two major questions remained unanswered

+ Can biotechnology provide a cheaper option than conventional processes?

+ Can economic gains and environmental friendliness go hand in hand?

‘The OECD Task Foice on Biotechnology fr Sustainable Industal Development has continued this wok, believing that

+ Biotechnology should be on every industrial agenda,

+ Significant environmental benefits can be realised

+ industal sustalnabilty Isa key parameter when deciding on process development

+ There is an urgent need to recondle economic, environmental and societal requirements in a

‘sustainable development framework

‘The present study secks to answer these questions on the bass of the experience of a number of companies that analysed the potential of biotechnology and decided to adopt o eject a biotechnology process tis based ona collection of 21 case studies, which are presented in a broadly similar format so that readers can easily compare one application with another All the available cases have been taken into account, though not all reflect successful application ofa new technology Two major types of biotechnology applications are covered, the use of renewable resources ("biomass") and the use of, biosystems (biocataysis, enzymes} in industrial processes

A very wide range of industrial sectors is represented: pharmaceuticals, fine chemicals, bulk chemicals food and feed, textiles, pulp and paper minerals and energy The range of countries is also wide: Austria, Canada, Germany, Japan the Netherlands, the United Kingdom, the United States and South Arica,

‘The principal audience of the volume is expected to be senior executives and members of company boards and government policy makers, One aim ofthe volume isto heighten the business

‘community awareness of biotechnology and the contribution it can make to the “Wipe bottom line”

by demonstrating what others have achieved and providing a process assessment tool to focus their decision-making process For policy makers, it seeks to provide a basis fr expanding the role of biotechnology and supporting the development of national RED and technology tansler programmes targeted at sustainable development, The assessment tool provided, the Green Index, hasa shortlist of key questions to be answered in any comparison and could be used by government authrities 3s par OF RED assessment

‘Fee Shell recent Connie Susaale Despont ~ A Managemen! Print

Se: Stelcon sllable om their Hera Meb

Findings fom case studies

As the case studies make clear biotechnology does not necessarily always offer the single, best route; sometimes it may be most effectively used as one ofa series of tools or integrated into ther processes However, the studies show that the application of biotechnology invariably led to a Feduction in either operating costs oF capital costs or both It led to a more sustainable process a lowered ecological footprint in the widest sense, by reducing some or all energy use, water use, wastewater or greenhouse gas production

‘The case studies suggest that decision makers regarded environmental fendlines as secondary

to cost considerations, but it is sometimes dificult to separate the two, since the reduction ofan input usually means a reduction in cost as wel Envionmental legislation can be adver for change, and legislative changes may widen the use of biotechnology without external pressures, environmental improvements alone are unlikely to lead

‘companies to change thelr production processes

{At the outset itwas thought that most decisions would be based on analytical processes similar to Iie cycle assessment In practice, the decision-making processes were as varied as the companies Involved Theretore,an attempt has been made to document these different processes

Companies rarely became aware of blotechnology and subsequently adopted it n @ systematic vay Biotechnology skills were often acquired by partnering with another company or an academic institute Once the skills were in place, lead times improved significantly for subsequent developments,

Government policy-makers can tip the balance of risk-taking, for example by developing a sustained, stable legislative base, offering financial incentives for improved sustainability and providing RED funding for bridging the enabling disciplines RED funding for sustainable development needs to be looked at carellly since, in many cases t

is spread over more than one ministry A further key role for government is in the field of, mahidiciplinany education particularly forengineers Conclusion and future directions

‘This publication takes @ number of steps forward in the debate on industrial sustainability, 1 produces hard evidence on the links between the two roles of biotechnology ~ environmental Friendliness and economic gins It aso gives a more precise picture of how decisions to adopt these new technologies are made by industrial managers The opportunities and constraints created by policies on industal sustainability are better understood All the case studies point to a future in which the use of renewable resources and the new biotechnological skills, such as functional genomics and pathway engineering, wll enable the manufacture of materials, chemicals and fuels in cheaper, more environmentally friendly ways and thereby improve levels of industal sustainability and quality of life generally ‘The next few years will see a number of major plants producing industrial materials and chemicals, from renewable sources, a5 well as the incremental incorporation of bioprocesses into a wider range of Industrial manulacturing, Any future publication on this topic should thus have a much wider range of

‘eases on which to base its analysis,

Chapter BACKGROUND AND AIMS

Introduction

For many yeats, the OECD has been a focal point for the development of risk assessment

procedures and the assessment of biotechnology’s potential to contubute to industrial sustainability

In 1998, the OECD's Biotcknolgy lor Clean indusinal Products and Procsss (BCIPP) identiied lie cycle

assessment (LCA) as the tool withthe greatest potential to provide a disciplined, science-based

nproach to measuring the benefits, environmental or otherwise, of alternative industrial processes

However although LCA offers great promise, the environmental and social issues peculiar to

biotechnology zequire special consideration Although ethical isues, risk assessment andthe economic

aspects of decisions are not stcly pat of an LCA any analytical tol, it isto be useful, must address

these Issues Moreover although LCAS may be considered helpful, they are used infrequently are felt

to be too complicated and to require data that is difficult to obtain

‘An OECD task force which continued the work on sustainable biotechnology has become aware of

‘ther comparative analyses inthis eld not necessarily based on LCA principles Those assessments in

the public domain can be loosely divided into two groups those undertaken by consultants or

academics to examine more closely certain environmental problems, and those undertaken by

Companies as part af a comparative analysis of process development Some of these may have led to

‘apital investment or RED planning decisions, others may have been used to seek approvals or grants

from government agencies,

Both groups of assessments were undertaken in ways that suit the needs of their individual

authors No analysis appears to have been made of their more general policy implications, nor have

they been brought together as case studies in such a way that decision makers, whether in industry or

government can easly compare the diferent applications

case studies

The taskforce established a project to bring together as wide a range of these assessments as

possible, in order to provide examples of how companies have approached the problem of making

tholces Its aim was to examine the data-collecting and decision-making steps employed by the

companies when adopting or rejecting biotechnological processes In cases where they have (or have

not) replaced more conventional physico-chemical ones The project's results are presented in this

publication

In all the task force collected 21 examples for which companies were prepared to make sufficient

ata publicly available to yleld a reasonable analyss While they do not represent a representative

sample in a statistical sense, they do cover a broad range of industrial sectors and many OECD

countries The preparation ofthe cases would not have been possible without considerable assistance

from personnel in the companies concerned and their help is greatly appreciated The companies

concerned have approved the case studies, but comments on them and inferences drawn are those of

the authou's) alone _mỊ

Le

‘Table | gives a breakdown ofthe cases by sector and county

Table 1 Cases by sector and country

‘catalysis provides strong competition Is also the case that choice ofa renewable feedstock does not

of itself guarantee sustainability Thisis particularly tue i fossil fuels are used during the manufacturing process [see the annex to Chapter? on bioethanol) Als, oll, ather than biomass, may be a more {economical source of complex monomers

Bor | The role of alternative technologies

No singe techlogy can give economic aceat oa ful ange of new products and thu tempting 9 fia favoured technology to.2 molecule or customer partcilary tue of chiral technologies where the pace of development Inthe international academic need fs therefore probably iljudged The it Eommurity such that any ner technology Is fall supplanted Fora new molecule entering the development phase, the need to produce kilo quantities quichly nny ounsigh economic consideration flows thatthe ranufectuing proces wed o this sage ent) biotechnology and physto-chemisty anda range of academic alaborations so aso remain uptodate An Sojuet tothe rok sthe ably to make rapid evabstion of ecm] options In some cases the optimal

‘evelopment path may include helping customers us element fhe toot in thet ow laboratories Ina recent development of weil intermediate fr an US-based pharmaceutical company, three sitemative approaches were used bioctalyin,symmetic hydrogenation and cystlization alo which {ave the product of acceptable qual The eneyme process was used to make tens of logs rears

‘The casestudies ate presented in a reasonably uniform format so that both managers and policy

makers can easly See how they relate to each other The analysis draws out the intemal processes that

lead to a decision and examines the technical and analytical methodologies used it identities the key

issues and lessons to be drawn from the examples, the decisions for which they were intended, how

they met the needs ofthe originators and how decision makers responded, Not all ofthe cases are

success stories ~ failures demonstrate some of the abstacies to adoption of new technologies and therefore add tothe value ofthe analysis

‘This publication seeks to make company managers aware of what has been done and to show that

adoption of biotechnology can have quantitative benetits Managers ate encouraged to look at the

‘Cases, o use the analytical tools suggested or develop their own, and to idently the analogies between

the cases and their own activities This should make them more comfortable with the idea of using

biotechnology: it should also show how they might compile new case studies both for internal use and

inorder to demonstrate to the wider public the “sustainable” characteristics oftheir company

Biotechnology canbe used to increase the sustainability of industial processes and to encourage a

shift in companies’ emphasis trom end-olpipe clean-up to inherently clean processes Several examples show companies moving back up the pipe by for example, introducing closed loop systems, This is a

‘smaller step than replacing chemical conversion with biocatalysis but sl offers a useful lesson,

‘These case studies make it possible to illustrate analytical techniques that may be af use both ta

industrial managers and government policy makers, To this end, a simple tol for prior assessment of

the enwizonmental impact of two alternative processes is described Itis Intended to identify the key sustainability parameters and provides an easy checklist for assembling the facts ofthe alternatives in

comparable form

This publication shows decision makers in government how forward-looking managers (the “early

adopters") have considered risks and advantages before ating They can then use examples presented

to make a wider range of industries aware of the advantages of biotechnology They may better

see which are the key issues that make or break an individual development, lear what they can da to

ease the climate for more sustainable processes and be encouraged to design polices that support

these decisions, The analyses are intended In part to support guidelines for the development of

national programmes and to allow individual countses to derive material eelevant to thelr paticular

reeds Governments can thus catalyse the spread of biotechnology: as companies see their peers

adopting they wll become more confident themselves,

Examples of what can be done by governments are given in Bot 2, These examples can be

repeated with variations in many ather countries,

This publication seeks to assist company decision makers through the individual stages ofthis

process because itis el tha: + In the first place, biotechnology should be on ever industial agenda

+ Eavizonmental aspects and customer perception issues related high on the lst of parameters, toa sustainable choice should be

Im addition, it seeks to encourage policy makers to

+ Translate environmental benefits for society ito economic benefits for companies by rewarding ‘good oF punishing bad environmental pediotmance

‘Establish a clear and stable legal and political environment in which the biotechnological alternative hasan equal opportunity tobe taken up

“+ Educate the general public to understand the risks and benefits of industrial biotechnology,

One limiting factr for confirming the potentisl of biotechnology isthe absence ofa scientifically

validated technique for measuring its overall long-term sustainability Joint govemnment-industy ation

to meet this need is essential to encourage consumer and public confidence in the resultant

technologies and, ultimately, to ensure the successful development and industry acceptance ofthe next

eneratlon of blo-based and cleaner ndusrlal products and processes,

yy

Box 2, Examples of programmes and initiatives

United Kinom The BIONISE Progiamme of the UX Depertment of Hade and Industry (DTI aims to

support the development af the UX industal bictechealogy sector and to simulate the use of proftabity by using biotechnology However many companies view biotechnology with eautlon and ae Unaware off growing use in manufacturing On completion ofthe std the ease studies la this eport

‘ll be esseminated fo UX companies in aerto help them addess ‘elevass tothe chemical sector will in addition be dasomtnated to induaty via the Speclaed Organic this Knowledge gap case studies of Chemicals Sector Assocation UmeringTechnaogies Group

Partnership seeke 9 matimise commercial benefits fom biotechnology and hae enti three core

‘hemes: discovering and developing new biecatalyss: developing integrated production processes and designing and modeling new and improved processes “The DM proposes to use the eave studia and ascent framework report to help advance the research, development, demonstation ceze=vmeal satuetae efbitectoelee le ccanerproducs and

‘evelopment Belglum ; The Flemish institute fr Technologleal Research (Vito) develops and evaluates now Insta technologies for effluent water weatment ard decontaminating polluted soils and dudee n this teseatch domain, Vito provides companies vith objective consultancy on the iatioduction of nvitonmentully tendly production and management techaiques and sistance with solving

‘Stvscnmcntal probleans Vito may bo 6 condu for ringing the cnc adios too wider audioncet

‘United State: During 1999 ana 200, the US Covernment ariculated 3 comprehensive “Bioenergy Iniiaive" to aecelerate the development of techologles for using renewable carbon asa feedstock for the production of power uel and products The intent to cteate a carbohydrate economy to reploe pot

‘tthe fal fla ed for theae sectors In 190, President Clinton signed bn executive order ad a 2000 the Sustainable Fuels and Chemicals Act an integrated pally to atimulote RED on renewables and blots, waesigned nol The Act authorced spending USO 250 millon over five years on RED alsa the congress am the prioiies fr RED spending and foster co-operation between the Departments oF ait and Ener Because a company’s performance is no longer judged by financial results alone, itis felt that

environmental assessment should be applied to all products and pracesses, large or small, in companies ofall sizes All stages of a products or process’ life cycle may allet the envionment Consequently, the design of industrial processes must take Into consideration everything rom choice

‘and quantities of raw materials utilised to euse of wastes, Environmentally Irendly processes will Consume less energy and raw materials and markedly reduce or even eliminate wastes As this publication demonstrates, biotechnology is capable of providing tools that help achieve these goals

nd, in the process, ensure that industrial sustainability is infact being achieved,

‘Sustainable development

In the 19705 and earlier, sustainability was one-dimensional ~it was equated with the profit necessary for a company’s long-term survival Later, environmental concems were added, and, in the 1990s a third dimension - societal concerns Hence the “tiple bottom ine" A valuable description

‘of what is meant by this three-part approach is contained in Cotinbuting to Sustaieable Deelpmcat A

LU Management Prier, recently published by Shell and available on thls Web site (au Shel 0ml

echaround Mote and more companies are adopting the principles of sustainable development in thele

everyday activities and see that doing so does not generate extra cost but can be an economic

advantage (see Box 3) Environmental considerations are thus not being addressed in isolation but are

‘becoming part ofa business's economic and social aspects

Box 3 Shells approach to sustalnable development Many sll question the wisdom of suiving to inteqrate the principles of sustainable development into

the way we do business Sustainable development requires ust think about more than jst How much ‘money we wil ake todo, butt takes broader view and balance the lng erm andthe shoa term We

‘las thc emphasis onthe balance betrecn the shat tert enllong term sự wel om the tegration of

the economic environmental and social aypects of our business For us sustainable development applies

Because sustainable development means taking a broader more integrated approach o ou business

Ir opons up excting busiess opportunites in emerging martets and new customer gloups sustlnable

development isatay of developing and saleguecdng ou teputalion, and it wil elp us develop out

besineses nln with Socety's needs and expectations ‘hell chatiman Sir Mark Moody Stuart sid na recent speech

Ne you sek to build your Business, standing ~ at were ~ on [soo each eg must be In place i

ou ate to bull on 3 nusanabe foundation The tly suranable development ofa sodety depends on

tives inseparable factors: the thee legged tool “The fst leg ite generation of economic wea, which companies delve better than anyone elie

‘The second is environmental improvement whore bath goverment andthe company have lo ply thee Tole The Ihr leg ts anal equity Companies have ee to ply here, bute nm feaponsibrty rots

environment i equaly senseless No mater how wealthy, a society fundamental lading la Cai equly

Sang be sistened

Entec, industry still lacks a clear understanding of the meaning of sustainable development From Nevertheless according to a recent survey by the environmental and engineeting consultancy,

104 companies surveyed in seven industrial sectors in the United Kingdom, including

pharmaceuticals and ol and gas, 45% of directors and chiel executives had not heard of sustainable

evelopment Over three-quarters (78%) of respondents thought that pressute for sustainability was

coming from regulators, an Indication that any moves towards sustainable development are likely t0

be compliance-deven, at felt thatthe result of sustainable development would be more costs and

additional work

The problem of management education, identified in previous OECD reports, is still ane to be

faced today As one interviewee put it, “Sustainability may well be understood atthe top levels in big

companies the problem is application and middle management has other objectives, The average

‘manager in a pulp and paper mill, for example, joined at 18-23 wit, perhaps, a bachelor’s degree,

worked in the plant forthe whole of hi life and is now 53 and only uses his own practical experience

‘gzined over the last 30 years A worry he has i continuity of production process ~ he doesn't want t0 Feport tothe board that there have been production problems hecause of the introduction of new

technology,

“6

Decision making

‘when an industial company decides to design and implement a biotechnological process to produce an existing ora navel product the decision is taken at a crossroads, where many different Information streams converge and from which a company may follow one of several alternative routes

‘The implementation of sustainable biotechnology solutions has been slower than it might have been partly because rea-Ile experience of its application is only slowly acquiced by and disseminated

‘mong companies One veason is tha the shift 10 biotechnology solution appears to the Industrial manager to have large economic implications and lage associated risks, [steady stream of innovations is emerging from academia, but these will not necessarily be taken

up by industry unless it is clearly demonstrable that they have a cost advantage Cost reduction can be dluect (lower matedal andior energy inputs, waste teatment costs, reduced capital expenditure) or inditect (ower risk tothe general publi, lower obligations in terms of eventual clean-up, contibution

to reduced global pollation levels, downstream recycling)

‘The decision to design and implement one manufacturing process rather than anther i always a complex one involving many parameters and is almost alway taken on the basis ofa less than ideal data set, Enviconmental benefits alone are not a sulicient incentive for adopting biotechnology Decisions ate much more Influenced by economic considerations, company statesy and product

‘quality ts approach to such a decision, a company needs to decide which parameters to take Into consideration economic (cost of production, Investments, etc, occupational health, eglatory aspects {product approval), environmental, customer perception, company profile and values and many others,

Te must then gather the facts together, making sure that it has access to comparable data for the alternative processes,

‘The lager the economic impact the more complete the required dataset Is likely toe, slmply because a decision with a larger economic impact merits a more thorough analysis, often through conceptual design or exploratory scientific projects to investigate the possiblities and consequences of different alternatives Although the costs may be assessed reasonably easily, benefits may be more dlfficule to measure, especially i the company is unfamiliar with the proposed technology and appropriate tools are lacking to allow ateliable assessment of the advantages and disadvantages ofthe new process

An essential rationale forthe use of biotechnology in industrial processes Is that It fs thought to bring greater sustainability and lower environmental impacts However this raises the joint problems of how to demonstrate that these changes actually occur and how to compare altemative processes while they are still on the drawing board Ultimately what is required is a framework of methodology, preferably internationally accepted, to evaluate biotechnology and bioprocess technologies with Fespect t0 economic and environmental costs and benefits Ih, thelr contribution to industlal sustainability)

By its very nature, the use of biotechnology, and especially of renewable raw materials, gives rise to

a number of speciic problems, Factors such asthe use ofa dedicated crop for manufacture rather than ood use and the elfect of widespread monoculture on biodiversity need to be considered Any detailed analysis may need to Include production inputs to agriculture such as seeds, fertlisers, Pesticides, cultivation, crop storage and farm waste management ‘hile environmental sustainability is only part of decision making, alongside economic and

‘operating considerations, itis likely tobe sufciently important to be examined on its own With easier [access to positive facts-based stories and with access to a simple "what-if" tool to assess the

‘environmental impact of process alternatives, t becomes easier to demonstrate the viability ofthe biotechnological option,

Chapter?

INDUSTRIAL USES OF BIOTECHNOLOGY

‘The applications of biotechnology fall conveniently into two distinct groups:

+ The replacement of fssi fuel aw matedals by renewable (biomass raw materials,

+ The replacement ofa conventional, non-biologcal process by one based on biological systems, ‘such a5 whole cells or enzymes used as reagents o catalysts,

Enzymes in this publication are recognisable by the fact that tele names iavarably end in “ase”

er example nae or celle) The nme of pectic mic-crgnas are geminal, as

Renewable raw materials

Use of renewable resources s very closely bound tothe price of the fossil raw materials they might

replace and sutfers when oil is relatively cheap Nevertheless, a numberof strategic developments,

especialy those sponsored by the US Department of Energy are taking place,

For some time, there has been increased interest and very substantial research Inthe production

of chemicals using renewable feedstocks, particularly in the United States, In addition to the

environmental attractions af using renewable resources, this has been driven by concems about the

‘dependence on imported oil, The United States is rich in the supply of renewable agricultural

feedstocks, such as corn, which can be used to produce low-cost starch raw materials

Living plants can be used to manufacture chemicals such as lactic acd, lysine and citric acid on a

commercial basis A novel approach to making plastics is to have the plant either produce the raw

‘materials or, more radically, to make i grow the finished product n 1999, a team at Monsanto used

rape and cress plants to synthesise a biodegradable plastic ofa type known as a polyhydroxyalkanoate

(PHA) by adding bacterial genes from a bacterium, Ralstonia caro, chosen because it produces high

levels of PHAs, into their experimental plants While bacterial PHAs are too expensive to be

commercially viable, those produced in plants should be cheaper Monsanto has shelved tis project

but tis stil being pursued by Monsanto's former partners atthe University of Dushar, England, and

the University of Lausanne, Switzerland In adllon, Metabolix (Cambridge, Massachusets)eecently purchased the assets from Onsanto in order to expand its PHA products BASF has also looked ata

related material, polyhydroxybutanie acid obtained from transgenic canola (rapel, although its

competitive wth polypropylene on an eco-efficiency basis, the net present value was regarded 2s too

low and the scientific isksin development were seen as 00 high

The development of polylactides offers a good example of a new process based on renewable

resources, Polylactides are biodegradable plastics with positive properties lor packaging applications

They ate made by the polymerisation ofa lactide that Is produced from lactic acid For many years

lactic acd has been produced by both fermentation and chemical routes Recently, developments in

the fermentation process and particularly in downstream recovery appear to have given the Bioprocess

an overall economic advantage as wel a the environmental benefit of being based on renevable raw

materials Cargill Dow Polymers (CDP) has announced the construction of a plant to produce 140 000 tons a year of polyactide using lati acid produced from corn by fermentation, The plant is

scheduled for completion inate 2001 (see Case Study 9)

‘To compete with polyester and other conventional petroleum-based polymers, Carll Dow Is locating its commercial-scale plant next toa low-cost supply of dextrose: Cargill corn wet-miling complex Cargill Do wll lerment Carglls dextrose to pure chiral isomers of lactic acid, a conventional fermentation route impossible with chemical synthesis, and then chemically crack the late aid into three chiral isomers a acide Finally the lacides wll be combined in various ways to generate a range

‘of polymers

Relying on dextose tes bioprocessesto com wet-mills in North America and, in Europe to wheat processors, but the ability to use a wider range of sugars is developing rapidly Carll Dow is exploring novel processes that would allow the use of feedstocks that are cheaper than dextrose, a capability that would cut the cost of making PLA as well as novel products Cargill Dow's next plant will not be so Timited The enzyme-converting technology and the ability to adjust fermentations to use a wider vatiety of sugars have all advanced tothe point where com wet-mils wll not be needed

Processing technology is already available to use sucrose from sugarcane, which costs about USD 0.03 compared to USD 005.00 for dextrose Cor br, which corn wet-ils sell locally 95

‘animal feed for 35 litle as USD 00/kg may be the next major raw matera in the United States, Corn fibre consists ofa range of fve- and six-carbon sugars, but RED on bioprocesses is being developed to ferment these Sugars Farm groups inthe United States believe PLA to be an important new market given slumping commodity prices and concerns over the safety of genetically modified foods Although Cargill Dow Polymer’ process uses fermentation, t does not depend on transgenic organisms because many micro

‘organisms already have the capacity to make lactic ai

In 1995 the US Department of Commerce approved funding fr a USD 30 millon five-year research project to develop continuous biocatalytic systems forthe production of chemicals fom renewable resources The project consortium led by Genencor, also included Eastman Chemical Company, Electrosynthesis Company, Microgenomies and Argonne National Laboratory There are signs that this project s beginning to yield results Eastman and Genencor have announced plans ta commercialise 3 new process to produce ascorbic acid using a specially engineered organism

'Genencor and Eastman Chemical, which holds a 42.5% stake in Genencor have developed a one- step fermentation forthe ascorbic acld intermediate 2-ketogluconic acid fom glucose, which replaces four steps in the conventional synthesis Two years ago, the firms declared their intention {0

‘commercialise the ketogluconic acid bioprocess, and they expect to begin the engineering work next

‘year Capital costs are estimated to be half of those fr the existing process, and low casts might also

‘open up new markets ey use of ascorbic acid asa reducing agent lt should be noted however, that

‘during the period of development there has been a significant reduction inthe pice of ascorbic acid Genencor has also been collaborating with DuPont on a bloprocess for the production of 1.3 propanediol PDO) directly from glucose The bacterium used as catalyst Incorporates genes from twa different organisms Significant progress has been made to improve the productivity of the {fermentation andthe associated downstream processing operations

DuPont formed a joint venture last year with Tate and Lyle Citric Acid, a subsidiary of sugar producer Tate and Lyle (London), ta demonstrate the feasibility of DuPont's bio-PDO process ona large Scale, The firms have already started a pilot plant to produce 90 000 kg/year of bio-PDO at Tate and Lyles subsidia, 8 €, Staley Manufacturing’scoen wetmill In Decatus illinois The fms plan to begin producing bio-PDO on a commercial scale by 2003 Meanwhile, DuPont is using chemically

‘synthesised PDO to build a market forthe PDO-hased polyester polytimethylene terephthalate (PTT) which the company markets as Sorona,

DuPont predicts that lowering the cost of PDO will broaden the commercial appeal of 3GT, a polyester copolymer of PDO and terephthalic acid, and also make PDO an attractive feedstock for polyols used in polyurethane elastomers and synthetic leathers ‘Chemsystems reviewed the alternative processes for PDO in late 1998 and concluded that the LIS biological route could compete with petrochemical routes if it was back-integrated to glucose

production om corn DuPont says further improvements have taken the process well beyond the most

‘optimistic case described in that study”

DuPont hopes that bioprocesses will enable it to produce compounds that are currently beyond

the each of industrial chemistry and has a wide range of industrial Biotech RED projects underway

The company, in addition to internal projects, has a number of other projects as part of a

USD 35 million, five-year alliance with the Massachusetts Institute of Technology DuPont says its in

the process of selecting a follow-up projec or large-scale development now that bio-PDO is well on the

‘way to commercialisation, For example, it has engineered another biocatalys or a diferent polymer

Intermediate, dodecandiolc acid, which is produced directly from dodecane

Since the late 1970s, a numberof counties have been involved inthe manufacture af liquid fuels

based on plant raw materials Production of bioethanol continues on a large scale in Brazil and the

United States, with more recent interest in Canada tsee the annex this chapten| while a wider range of

countries are exploring the potential of biodiesel

In March 2000, the US Department of Energy announced a tripling ofits budge to USD 13 milion

in 2001, for its bie-feedstock programme Companies such as Dow Chemical, DuPont, Great Lakes

(Chemica, Eastman Chemical and Rohm and Haas are part ofthe programme The programme's aim isto

Increase substantially the numberof chemical processes using bio-feedstock and could lead, according

ta the Department, 10 reduction of tens of millions of tons of greenhouse gas emissions,

The Biomass Research and Development Act passed by the US Congress last year allows the US

Department of Energy DOE) to place equal emphasis on biomass as a source of raw sugars for

chemicals and an lowering the cost of bioethanol fuel DOE expects enzyme producers to lead the cst

Improvements In particular, cellulase costs must fall tenfold, from USD 0 30-0.40/gallon of ethanol

produced to less than USD 0.05/allon, before biomass conversion becomes profitable for large-scale

ethanol production, in 1999, DOE signed three-year contracts with Genencor and Novorymes

(USD 17 milion and USD 15 million, respectively! to achieve those cost improvements Like logen in

Canada, Novozymes and Genencor make cellulase enzymes for textile and pulp processing Novozymes

wil try ta make currently known cellalases more active but will also search for navel enzymes that could

assist the process, The intention isto genetically engineer all ofthe necessary steps into a single

siganlsm

Cop enhancement may eventually cut the cost of making a wide range of chemical products

Several lirms are seeking to make high-value proteins in crops Prodigene for example, has developed

2 com variety with the genes for avidin, an egg white protein used in medical assays The company

intends to commercialise another protein, a bovine protease inhibitor, aprotinin, used to prevent

protein degradation during cll culture, Large-scale production in corn can greatly lover the price, since

fading capacity is elatively easy Prodigene is also working with Genencor to make Industlal enzymes In plants The companies are particularly hopeful about applications in which an enzyme-enriched plant

could be added directly to an industrial process, eliminating costly purification steps

Bioengineering of crop plants wil improve the markets fr oils and fatty acids, DuPont, Monsanto,

and Dor are all marketing vegetable oils enriched in oleic acd Crop developers hope to manulacture

Speciality olls for Industral applications, though limited funding for preduct development and higher

than-expected costs are slowing development,

DuPont is explaring application of its high-oleie soybean ol, which can be chemically epoxidised to

form nine-carbon diacids for plasticisers, and has cloned the genes needed to epoxidise fatty acids into

the plant ths also cloned the metabolic machinery to conjugate fatty acs for coatings or hyeoxylate

them fr lubricants,

Monsanto has engineered rapeseed cil for industrial uses, enriching the oll with laurie acl for

surfactants, myristate for making Soaps and detergents and medium-chain faty acids for lubricants

However, Monsanto has given these applications low priority in arder to concentrate on health and

Pharmaceutical applications The spin-off of Monsanto's agvo-business, following a planned merger with

Pharmacia and Upjohn, could restart the project

Bisetanglser

—ị

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DuPont believes that production in crop plants is inevitable, because thelr feedstocks, carbon dioxide and sunlight, are essentially free, At the same time, biotech firms such as Masygen say there is plenty of room to improve and extend enzymatic catalysis ad fermentation,

Bioprocesses

Although enzymes have been used on an industrial scale, in detergents for example, since the 19505 full acceptance of their oe in biocatalysis has been move recent, withthe lead coming rom the fine chemicals industry Man’ of the drawbacks perceived by process engineers, such as low yields

‘and throughput, high dilutions, limited enayme availability and low enzyme stability, have largely disappeared Itis now accepted that water may be a suitable medium for industrial processes while at the same time enzymes are being modified in such a way that they can be used inthe organic media

‘ith which chemists are more familar

‘The advantages of bioprocesses ae generally thought to be that they operate at lower temperature and pressure, while chemical processes require harsher conditions, and that enzyme catalysts are biadesradable after use but inorganic catalysts are more dificult to dispose of However, bloprocesses

do not always have advantages over thei chemical altematives and its necessary to determine which process perlorms better on the basis of careful examination of the merits and demerits of each, A.wide range of reaction types ~ oxidations, reductions and carbon-carbon bond formation, for

‘example = can be catalysed using enzymes, and perhaps 10% ofall known enzymes are available on an industrial scale These may be used as free or immobilised whole cells, crude and purified enayme reparations, bonded to membranes or in cross-linked crystals Many are based on recombinant

—

‘The potential for discovering new biocatalysts I stil largely untapped, since 99% of the microbial

‘world has been nelther studied nor hamessed Recognised through thelr DNA sequences, members of the Archaeal and Eubacteral domains are expected to provide biocatalysts of much broader utlity as this microbial diversity is futher understood

Two quite different approaches to novel enzymes exist each with ts supporters One i the rational design approach, whereby knowledge of existing protein structures is used to predict and design modified enzymes The second is forced evolution, in which many mutations and recombinations are made and screened for selected properties, The combination of these techniques together with detailed sequencing of the genomes ofa ange of organisms, i giving rise to tailored microbes capable

‘of producing many new and existing products for which only chemical routes have previously been available Gene shuling in which DNA fs denatured and then annealed in novel recombinations can {ive unexpected results For example, starting with 36 sources ofa protease enzyme, shutling Hise toa library of 654 variants, % of which are better than the best parent In another case, shuffling, produced a progeny enzyme with properties possessed by nore of the parents, In this case a heat- has given

‘table lipase In the most exciting example to date, the genes for just two enzymes difering by only nine amino acids were taken, and in the recombinant library produced from these, there were enzymes With atvities inereased by two orders of magnitude and some entirely navel catalytic activity

The combination of renewable raw materials and a novel process can have important economic advantages (see Box

AS mast, If not all, novel technologies go through a typical S-curve in their development, it should

be appreciated that industial biotechnology is stil near the foot of its growth curve As chemical products become more divers, the synthetic tend is shifting fom stoichiometric synthesis towards Using the complexity of biological systems ~ moving from blocataysis and biotransformations to direct fermentation (metabolic pathway engineering! and the industrial applications of “biosynthesis on a chip* and from single synthetic steps to cascade catalysis in which a umber af enzymes act in concert Without the need to add and remove protective groups,

In the next few decades the DNA of al industrially Important micro-organisms and plants will be sequenced and their gene steuctures defined, thereby allowing metabolic pathways to be optimally

Bisetanglser

Bor Lysine feed additive Midwest Lysine LLC a joint venture between Cargill and Degussa, has bul lant i lai,

‘extrose aw materia the Iyin wil be used sea feed additive fo increase the nutlonal valve of

Plant proteins Lysine has been produced for many years by fermentation, using Cone of Brevbueria The

conventional products Lijsine-HEl which produced b) amulstep process When Degussa decided

to'become a prodacer it ealed thatthe “conventional” process would be very expensive, becauce ol

|New product, Rolo, was developed, anda new process was invented and patente by Deeussa

that reduces the by-products and the wastes almost fo zero Degussa changed fam materials and

fevmentation process so thatthe fermentation bath conti lysine nd by-products auch aati that

the product hese sine when died Because sucha fermentaton bth very difialt tody special technique had tobe developed which esltsin a granulated dust hee product

ro wastes are produced This an example of low-aue bulk product which would never have Been

conomical without such saving ‘The USD 100 millon plant which employs 70 people, began operations in une 2000,

elicient Metabolic pathways willbe thoroughly understood and fully functional quantitative models

will be available Very low-cost ray materials for bioprocesses will be derived from agricultural and

forestry wastes and, to an increasing extent, cultivated feedstock crops Known biocatalysts will be

improved through the application of molecular biology, genome sequencing, metabolic pathway

engineering and directed molecular evolution

The diffculty perceived by the new biotechnology companies lies In persuading chemical

engineers ofthe advantages ofthe new approach In practice, this may mean demonstrating a process

at large fermentor (small pilot) scale One company with long-term links to major intermediates

producers claims that if it knows a company’s ideal process parameters it can provide an enzyme to

meet those needs The idea of adjusting a process around an enzyme tends to put off chemical

Companies and therefore the enzyme should be optimised tothe process, What properles~ stabi

specificity, activity insolvent, temperature, etc, ~ are Important? I is now possible to search for

multiple properties simoltaneoussy

In parallel with developments in genetic engineering have come improvements in biochemical

engineering that have yielded commercial benefits in reactor and fermentor design and operation,

Improved contol techniques and downstieam separation These have resulted in move rapid delivery

of products tothe marketplace, As the examples inthis publication show, i na Tonger the case that

biotechnological solutions are relevant only to high added-value products such as pharmaceuticals,

Bulk chemicals, including polymers, and heavy-duty industrial processes may have a biotechnological

component

‘The international market for bloproducts and processes is increasing rapidly, Natualy the lea Is

coming from the pharmaceuticals sector In which foal biopharmaceutical Sales reached USD 13 billon

in 1998, an increase of 17% over the previous year Outside the pharmaceuticals sector, the Industial

tenzyme market is estimated to double in size from 1997 (USD 400 million) to 2004 Currently

bioprocesses account for commercial production of more than 15 million tons a year of chemical

products, including organic and amino acids, antibiotics, industrial and food enaymes fine chemicals,

aswell as active ingredients for cop protection, pharmaceutical products and fuel ethanal ay

‘The nest generation of bloprocesses will target large volume chemicals and polymers and will compete directly with petroleum-based products, Bioprocesses are becoming competitive with conventional chemical routes, but industry experts believe that further improvements in enzymatic catalysis and fermentation engineering may be required before many companies are prepared to

‘announce world-scale bioprocessing plants, The competitive edge may ultimately come from the

‘development of bioprocesses that use cheap biomass feedstocks such as agicultual wastes rather than the dextose that is curently the pretend renewable raw material

Biotechnology products must compete in economic terms; itis not enough to be environmentally preferable Cargill Dow's polylactide (PLA) is being brought to markt strictly on the basis of price and Performance because customers will choose to buy based on value For example, indigo dye Is Conventionally produced via a haish chemical process Genencor succeeded in modilying the metabolic pathways in E cl to make indigo by sing ita gene trom another bacterium to make the enzyme naphthalene dioxygenase However, by the time biovindigo was ready to be marketed in 1997

‘competition from China had eroded the price of indigo by more than 50% and mill were not willing to

ay the premium price Genencor needed to justly investment in acommercial-scale operation Bioprocessing proponents see a future in which micro-organisms are replaced by purified enzymes, synthetie cells or crop plants Biotechnology firms are adapting enzymes to reactions with greater Volumes and more severe conditions than those involved in the synthesis of fine chemicals n 199, Dow Chemical signed a three-year, USD 18 millon RED and licensing deal with biotech frm Diversa to develop novel enzymes for Dow's production processes The companies have already optimised an

‘enzyme for a dehalogenation step in Dow alkene oxide process, Dow expects to pilot-test the new

‘enzyme by early 2002,

‘New participants, Including established firms such as Celanese and Chevion, ate beginning work

‘their ovn bioprocesses through agreements with small spedalist companies that have developed tools for metabolic pathway engineering Celanese, for example, has established royalties agreement with Diversa because the latter has the ability to “genetically engineer the a research and metabolic processes of an entire cell to perform the desired reaction’ Chevron Research and Technology has entered into a thiee-year agleement with Matygen to develop bioprocesses to replace chemical processes, including the conversion of methane to menthanol, and Hercules has signed with Maxygen to gain access to Maty gens gene-shallingcatalyst-optimisation technology, Maxygen also has

‘commercial inks with Novozymes, DSM Pfizer and Rio Tinto, while Diversa has similar arrangements with Dow, Aventis, Glaxo and Syngenta,

Diversa recently agreed to watk with Novartis to commercialise enzymes for use as animal feed additives and to develop genes that enhance crop plants It also optimised a heattolerant enzyme, discovered in a micro-organism cotonising a deep-sea hydrothermal vent, for use by a Halliburton Subsidiary (Halliburton Energy Sersices) to enhance al eld recovery, Diversa is producing forincorporaton in Haliburton Energy Services's facturing Maids, the enayme Maxygen is using its gene-shulfling technology, which rapidly generates variants of gene sequences, to help Novozymes optimise industrial ens}mes for detergents, food processing and other applications, and to improve antibiotics production for DSM, Maxygen says It ill soon be feasible to

‘eaten entyme as required rather than optimising existing enzymes or ndustal conditions

‘While major companies recognise that products must succeed by competing in economic tems, advances in genomics and genetic engineering, coupled wit increasing environmental pressures, mean thatthe competitive postion of bioprocessing return to the marketplace will continue to improve Perhaps even bio-indigo will La

Annee BIOETHANOL,

A combination of national security and the nee to meet aigets agreed under the Kyote Agreement it diving

s thie wave of terest in Bloluc= parieaal bioethanol Low etbon emissions scanarios eet the emergence

‘Stethanal ae significant rource of fel both forthe transportation and Industral sector: Inthe longer ttm 3 Zevo-emission ethanol fel could be produced from sustainable agrculfural and biomass sources Comstarch

[United states) and sugacane (Bra are presently the major sources af ethanol, which i either blended ith

peti or used on ison “The United Sates curently has feel ethanol plans producing 5 67 bln lines per year The leading states

nots wth 225 bili tes, y ate August 200,15 new pants wee projected in 1 tates witha total capac of

2 lion ites nthe United States, 12 of ptt s bended wh comderved ethanol AI ngjor vehide manufacturers warat their cvs for use of E10 fel (10% ethanol + 0% pet) Many

rmanlacturer ate to producing libel Yohies(FFY) with engines capable ol scepting blends up 1 5%

‘ikana: Over {2 milion £95 veils (5% ethonl FFVS] were in the US Hest Fl be bling I milion £85 veces in sping 200189 200, CM predicts

The use of omstich wil always have ta compete with llematve food and eed wes, otha most interest

stow dimciedIowards the Use of calluose kem taste kiemes bom ket trảne Đrin pehdudiem the

Comm ethanl plants use coal or naural 4 to fuel their ditilation process The CO; produced by thi

‘omburtion har to be taken into acount vien etimating emissions of greenhouse gases (CHE) In the transportation sector The levels of CO, emasons fa damavealy when the ware lignin rom lignoelsone rs

Iiaterats sued as uel Ins 1997 scenanos the US DOE made estimates oO; emissons om transportation fel

“The Government of Canada's Action Plan 300 eq Climate hangereletzttenienffontomteetCAD 00 milion

‘over the next ive years Thi together uth he CAD 62 milonin he 2000 budget, represents commitment ver {ED Ibn in speaic actions te reduce GHG emissions by 85 mewatons a Year The iatives outlined Inthe

‘Aton Plan wl ake cana ane third lhe way to ehieving he target established ‘canada has ageted transportation whichis cantly he largest source 25%) of GHGs in the Kyoto Proto asa key sectox Without

further action, Hs fom thi set could be 32% above 1980 levels by 2010 Canadas caren annual peel

‘consumption i 2530 bilo lites, of which E10 Measures inthe Aion Plan inl increasing Canada

“The province of Saskatchewan (Canada) estimates that it has enough waste biomass at present, some 2 millon

tons, t9 produce & ilion liver of Kel ethanol However ung hybrid poplars and other acuta ello his

‘ould ce 195 ln ites, without any Fedtion of ood wal production Neither commbased ethanol no ethanol fom cellulore are economically competitive with petal Beare the

Inteducton or organisms capable of fermenting multiple sugars, ethanol fram biomass wa projected to con

USD 158830115809) he 1905 the ox fel foUSD 1.16 per gall The propane forecasts afllto USD 082 ay

‘umber of other Us regionshave chouen to use RF with the consequence tht according tothe EPA one-thid of

‘iI petcl sold in the United Sates 2 RPG RFC contains various compounds contafing ctygen Thon 23 Suygenates) in the Chicago aes over S0% ofthe oxygenate is supplied ar ethanol As well a reducing emissions, RFE ongenater displace the carcinogen, Benzene found in conentonal pete! Total VOC emissions in ontbated 278 ofthis dop In emiesione In he 19905 the Us Depart of Energy National Boel Progam focused on developing new, te vesatle

‘mige-ogansms to ear more ethos! rom biomass The progommes mission isto develop costae,

‘svitirpertly canh loi fr predecion of eltematie Gaytstation hcl sân he Fan li bireee The esl te deco tclcbogy that cn wll: mow-ied anions ef snp cthanel pric, Asditonally he programme hae collected ngotus material and energy balance data to give increased conisence 1a projected Performance and cost eves Recent esearch has focused on cellulase enzymes, Works ao targeted at organisms capable of converting all the sugars in biomass especialy the pentose sugars Alena svatgis Include the use ofthe Ea worse

ty addng the capability To make cthaaltostain which can metabolic ange ofsugars, andthe ation ofsugat

‘metabolism o yeasts that produc leehe The prograrme is supporting wath a the Univers of Miscansin and

‘ironto to crdinte both aeastauain aod arctominan lnm of thc erpniam Zpmements developed by DOE

Le

Chapters ALTERNATIVE TECHNIQUES OF ANALYSIS Deciding whether or not to adopt a new industrial process, be it based on biotechnology ot conventional physics and chemisty, requires a number of Important decisions Howeves, the point at hich these decisions are taken isthe crossroads where many diferent pleces of information converge and where a numberof alternative routes appear Steps leading to a decision might include:

+ Getting the idea Can the company make money producing this product the new way?

+ Setting the agenda forthe decision Does biotechnology get onthe agenda at all?

+ Setting the agenda I Which parameters does the company take into consideration? Economy (ost ‘of producing investments, et}, economic risk, occupational health, regulatory (preduct approval

‘environmental, customer perception, experience base, company profile and values, ee

+ Getting the facts together Economics, sk profile, technology base, etc Does the company have ‘2¢eess to comparable and solid data forthe alternative processes? + Looking tothe future Does the company feel confident that It can predic the legal envionment ‘and the stakeholder conceras? + Decision

+ implementation

Looking atthe whole picture

While environmental considerations are an important subset ofthe parameters to be considered in any process analysis (sce Box 6) they are only that a subset Areas such as operating costs or process Conttl aren principle, as important, although, fom the early 1990s, environmental risks began t take

‘on greater importance

‘Tete sa need to see the total picture — only if other parameters are at much the same level can fone look at environmental Issues, Previous OECD work has shown that there isa steady stream of biotechnological innovation, but this is not necessarily taken up unless i has a clea, demonstrable advantage, which is usually cost-based Cost reduction can be direct iprocess capital expenditure or

‘operating costs} or indirect (reduced risk to public and environment, ower clean-up obligations, lower

‘slobal pollution tates te)

Techniques for comparing alternative praducts and processes need to address economic considerations such as capital expenditure and operating costs: supply of raw materials (availabilty and security|; processing considerations, suchas the ease of integrating anew process element into an existing operation or onto an existing site: the nature of the marketplace and the activities of the Competition Inthe marketplace, for example, i there a need for world-scale plants or could the market

be better served by smaller modules more conveniently located

Process Profile Analysis [PPA, as used by DSM, i an example ofa technique that may be used at

an early stage of process development allows for the brainstorming of perhaps ten ideas and the Feduction ofthese to two or three for futher consideration (see Box 5) Alternatively it may be based

fn an existing process with other possiblities to choose from or on rating one's process a competitors

‘The technique can equally be used for several alternatives an one site or the same process at diferent locations PA is ordinaily a paper exercise, Whether itis suitable fo large volume bulk chemicals Is less certain These may require indepth analysis because the likely capital expenditure figures wil be very large,

Box Techniques for process analysis,

Many large companies have developed their ovn set of techniques to analyse new of competitive processes in their ea stages of development DSM inthe Nether, for seampl, has eto our {ols they call Process Profile Analyse (PPA), Technologiesl Aesensment, the Cost Curve, and the Experience Cure POA selects ive or so ey parameter, gives them weightings which ay dif fo diferent mat sects and gives each parameter a scare fom ane to ten Atematives ae ikl to have dilerent sores thd hence be a beter or wore cote, Technological Asessmeat scpurtes the xed and variable cost of alternatives onan equal tonnage mach the same for aiferen technologies rom competitors Prasutviy [veld per given volume) fea

‘ory important parameter especialy when companng bioctlyts with conventional chemist) Finally, Experience Curve, a progression rom conventional “s-cuves, plots lo constant money prices agus og cmultive volumes ivevitaly a negative lope straight el and asks whether ny Be

‘resisting technology can met the expected alin pce

A set of agreed parameters, which are given diferent weightings for each market sector, should be chosen These might be, for example: operating costs, capital expenditure, process conto, internal fisks and external sks Each can be subdivided Internal risks, for example, might be waste streams land health risks, while external sks might be avallability of key materials, new lavs and regulations

‘and patentability of ideas,

BASF has developed a similar process, called eco-ffciency analysis, which is used to compare processes and products So fs, they have conducted over 100 analyses, including 50 in conjunction with thelr customers, This technique takes into account the views ofthe end uses, Life Cycle Assessment Isee below), total costs and environmental burden, Another company among the case studies has set up a business and technical team in which the commercial group look at costs, quantities and profit, while the technical people look at how to make the product Possibilities are brainstormed to decide which process to use and how much time and lab effort to spend In this case, environmental impact is a key element inthe analysis, all processes are assessed for eluents using a decision tree process in which a weighting is given to each effluent

‘which is then incorporated inta an overall evaluation of each process's attractiveness Negative factors do not create a problem if they can be adequately dealt with Energy consumption is not considered under an environmental heading but rather is an economic factor considered as part of plant occupancy, All altematives should have a level playing eld, comparing like with ike, Thus alternatives should

be imagined as being on the same site, manufacturing the same quantities of product The problem of

22 missing process data should be addressed and should not be an excuse not to do the analysis The

exercise can always be repeated when new information becomes available, Then, together with

experienced process engineers, a hypothetical plant should be buil foreach process

The result may be that no distinction between the process alternatives is found, This may be avery

Important conclusion: it shows tht the route to the final produc snot the deciding factor, so that other

socio-economic parameters are more important

Based on the information collected inthe analysis, a trend between price (corrected for inflation)

and market volume can be constructed Extrapolation into the future using the estimated increase in

‘market volume gives avery useful indication of future market prices,

This chapter does not set out to be a text on capital investment Rather, it concentrates on the

limpact on the decision-making process of envionmeatal considerations, both local and global, and of

environmental legislation The principles are simple and are relevant to all activities and sizes of

company Its the evel of detail tha should always be adjusted to ensure fitness for purpose The goals

include comparing altematives to allow the selection of options with the lowest environmental burden

while meeting established standards of safety, quality and cost and identifying an environmental and

economic optimisation ofa present process It should be remembered, however, that assessments

always need to be Integrated into other management systems if they are done merely to obtain 3

Permit to proceed, for example, much ofthe ello and information could be wasted

Life cycle assessment

In order to evaluate the best process, itis necessary not only to examine individual reactions but

also the entire process Irom raw material supply to final disposal ofthe product As shown in the

following diagram ofa hypothetical bioreactor process, each ofthe processes requires the treatment of

‘aw material, energy intermediates, by-products and waste, Thus, one eificient process may affect,

thers adversely, resulting in worsened overall elicieny

Of all ofthe methodological approaches to assessment, LCA has been identified as one ofthe most

promising, LCA is a way of evaluating the environmental impact of altemative products and processes

Figuo 1 Bioreactor process

In terms oftheir enesgy and materials taking into account the entire lifecycle ofa product ot process: Irom “the cradle to the grave", While this publication i primarily concemed with altemative processes, most LCAs are cancemed with products, An LCA includes the production, the use of the product and its disposal Because itis global and holistic, this type of analysis offers away to:

+ Decide whether a product, process or service in fact reduces the environmental load or merely "wansfers It upstieam to eesource suppliers or downsteam to treatment or disposal stages + Determine where in a process the most severe environmental impact if!

+ Make quantitative comparisons of altemative process options and competing technologies The ideal way of comparing the environmental impact of different processes is to elaborate detailed LCAs foreach alternative At the early stages of process development, however, the level of

‘accuracy and detail required by a taditional LCA may be too high and therefore too costly to generate, {and much ofthe infmation requited may not be available Instead, a qualitative approach using a relatively short lst of parameters can provide valuable feedback AMLCA can be conducted at thee diferent levels depending on the purpose and application: + Conceptual LCA s the fist and simplest level of LCA ~ it may be regaled as life cycle thinking [At Ths stage the investigation Is used to make assessment of environmental aspects based on 3 Fimited and usually qualitative inventory The results are often presented using qualitative statements or simple scoring systems The study canbe [and is normally limited with respect to phases as well as parameters An example of the use that can be made of such a first stage

“inventory” can be seen in Cail Dow's Web site, which shows their approach (see Case Study 9) tothelrnew polslactide biopolymer (wns cdylycomipd 30103883 pd,

Simplified LCA, also called "Screening LCA” or "Streamlined LCA", covers the whole life cle = asdoes a detailed LCA ~ but at a more superical level A simplified LCA aims to provide essentially the same results as a detailed LCA, but witha significant reduction in espense and time, To ensure that the overall result gives a true picture of the impact, a quality check of the data is necessary Roche has carted out asimpliied LCA on thelr product ibolavin (see Box 6), land BASF AG also reports a similar approach to compare indigo manutacturing and dyeing, processes in which the indigo may be synthetic, derived from plants or produced biotechnologicaly naw es deewumeelootefzer

Detailed LCA comprises a complete LCA kom “Ihe cradle tothe grave" Nowadays, computer soliware, such a8 the SimaPro programme developed in the Netherlands (see Bos T and Case Studies 15 and 20), is available to ease the task of performing a fll LCA The International

‘Organisation for Standards (ISO! has published a number of documents relating to detailed LCA

‘methodology (ISO 14040-14083 cover principles and framework goal and scope definition and Iie cycle inventory analysis, fe cycle impact assessment, and lite yee interpretation),

A numberof software programmes are available for LCA analysis, each with its own strengths and weaknesses Such software simplifies the work of analysis follows corect LCA procedures and correctly interprets the cause and elfect chain of any pollutant, They are useful tools fr mapping out the overall

‘environmental impacts of production trom the cradle tothe grave They can help to reveal the steps in the production process that are crucial for environmental improvement and can illustrate what replacing

‘one product by another really means forthe environment, The databases, however may include data from only one region and may reflect the practices ofthat region Other software may have databases

‘ith information that is more appropriate to the location ofthe new process

It must be kept in mind that the calculations for a complete life cycle are done on the basis of a range of assumptions and diferent data sources, In particular, alternative manufacturing routes need t0

be investigated and compared atthe same level of detail

Sometimes, no data on the environmental loading ofthe process are available n practice, they are

‘assumed not to exist This can be important fr the results and conclusions of a comparative LCA, ifthe

28 gapsin one alternative ae more important than those in another, However, important gaps may be

Box, Life eyle analysis of riboflavin manufacture och has ciel ut an in-hiss LCA of the chemical Wolgial rice or thơ mandadure

Considered as faw materials The various ecological parameters were chosen and compared with one

Snother on the bass of 16014040 ff The results have been documented in such s ay a= to make 3

emparson of the ecotfiiency and sustainably e the te processes as comprehensible as possible to

Streader public aw ruterinl: The Kclogcal pce vege 15 tte mcf aerial ial bu cay

Water consumption the biologial process requltes about double the water but the greater pat of

this Isforeooling and fot punted The amount of process and waste treatment water nthe chemieal

lowes seven times a high ‘Energy Soth processes use about the same quantity of energy The proportion of high-value

lect lor sting, cooling and evaporation a about double i the biologie procesn but steam and

‘atual gue consumption in scduced and thus the CO, emissions om lol fel combustion ate alsa

“Emislons tal: Particulates fom produt formulation ate comparable, Solvent ate emitted at each

stogs atthe chemical process ‘The late also ves ot odours, which ate reduced tothe necessary level by scrubbing and adsorption and in total these are double the ethanol emited by te biologi process

0, emissions tom both fermentations botavn vs ribose) are envtonmentaly util since this

‘gully of CO, is ned in photosybens to make the gluoue raw mata

procers The eater om the latter contain Inotgani salts and feds om eanly Srodegraasle

Elomass, while ‘Soll waste The slid waste fom the biological proces exclusively biomass, wich s retuned the waste rm the chemeal process so contains ogame chemicals a @

rnutient tothe sol eter composting The compost contains mast of the nitogen and phosphorus utente

Used in fermentation The chemical proces produces, n addon toa seller emeunt of bamass slid

‘hemi wastes dition nd ler residue) which te incinerated in an appropeteinotaltion

"Transport Individual stages ofthe chemical process are not caried out inthe same plant and

lnsermediates "Bo kao" CO; perton a product om fossil fel combustion are therefore tansported fom enelecalon fo another Ths anspor ves Hse to an ews

Box 7 LCA software Simatro 40a sfteare tol developed by PRE Consults Bn the Ntherands to simply the work

ofan tea Each process is represented by a data shea, which contains ll normation received on inputs aw

‘mateal ipa eneray demand outputs tom other processes and autputsfemistons ad products le

‘With this ntrmation about each process ands procees re of the le eee, Simao abe to ram

Up a inventory all the environmental inputs and outputs ezecsled vi he produc

ae based ane theory fdistance Enrope, while the other dats policy levels insead of sustsnabity levels Policy level ae sally 9 To target In one the target cderived fom real enirnmental data for

ompromise between politcal and entonmental considerations

Le

Aled either by additional data gathering or by obtaining the mass and energy balance through process

simalation

A checklist for sustainability

The Green index (see the annex to this chapter! is a checklist or adeno for industrial managers

at the "Conceptual LCA” level that provides a shorlistof key questions to be answered in any ompatison, A number of companies, uch as Genencos, have developed similar approaches for thele

‘on analytical purposes, Possibly the most authoritative version ofa conceptual LCA will be contained in 80 documents which are expected to be published shony

‘The Green index is used 3 follows

+ Processes to be compared should first be *nomalised’ In other words, they should be compared on the basis of the same amount (or value) of the product resulting rom both processes, made on the samme location, When collecting information tis cially imponant that the data set chosen should be as comprehensive and reliable as possible While the accuracy of the data need not be high, all parameters considered relevant must be included

+ For each of the parameter, data are collected foreach altemative process and evaluated on an “order of magnitude” scale one ofthe processes is clearly superior (uses less ofa non-renewable resource or produces less waste, fr example, it should receive a postive score Ifa parameter is hard ta evaluate because of lack of confidence in, or non-availability of data then this becomes a sign either to improve the data or to make the judgement that the particular parameter is not

‘relevant, All such decisions should be documented and the process contiaued untl all parameters hhave been included The evaluation should be repeated foreach alternative process

+ tfthe total evaluation yields an ambiguous conclusion, if, for example process ‘but produces more solid waste than process B, this indicates that i is necessary elther co do a A uses less eneray more thorough analysis (a simplified LCA, for example! or to accept that the change in environmental impact will not be the decisive lactr inthe choice between the alternatives

+ In more detailed analyses, waste should be weighted Thus, heavy metal wastes should have a strong negative weighting followed by solvents (which ae recycled as far as possible), by other Inorganic wastes and finally biodegradable wastes Waste safety, for example in terms of toxicity tofish, is important where eluents are discharged to vers

‘The fnventory of inputs and outputs should be chosen so as to provide the necessary data for assessment of most potential environmental impacts ISO has published a preliminary list of potential impacts of a new process of product, but it should be stressed that only certain subsets may be relevant, Moreover they may only need to be considered ata relatively late stage in the analysis in relation to adetalled LCA The 150 preliminary isis follows

+ Abiotic resources limited resources

+ Biotic resources isustainable/non-sustainabe use)

+ Land use,

+ Global warming

+ stratospheric ozone depletion

+ Photochemical oxidant formation

‘At the conceptual level, sa fll sk assessment needed? At the “paper and pencl” stage, it may

‘only be necessary to ask how legislation, curent and foreseeable, might apply to alternative processes

[Ata minimum, any new activity should comply with all local and national legislation Decision makers

should focus on the main features of the system that have environmental implications and adivst the

reporting precision to the weakest data to avoid creating a false sense of accuracy

High temperatures and pressures and the risk of explosion are not necessaly isk factors since

they canbe translated into investment decisions

Before moving to a more detailed stage, i is important to realise that the lst of environmental

Impacts may change during the course of analysis It may also be unmanageable when it has to be

applied to every reagent used

oy

Chapter LESSONS FROM THE CASE STUDIES

‘A numberof significant general lessons may be drawn from the ease studies in this report

“The first is that the application of biotechnology has invariably led to a process more ‘environmentally friendly than the one it replaces This appears to be the first time that this has

been quantified

+ Another cruclal message Is that the role of environmental effects tends to be secondary to ‘economic and product quality factors when companies consider adopting a new process Only

Box 8, Water recirculation in the paper Industry Process water use isa major cost element in many industries, partcularly with respect 1 waste

treatment, bocause of ever ighter dacharge lite While past investnent hes focused on end-olppe

treatment indus is more and mare looking to inestted water management and ultimately to closed

mate etter ne of auaable water The fst quenton fo be asked in ny paper mls can mowed Toop

Botopeal system be Introduced for water re-celation? ‘Anaerobic up lew sludge blanket (UASB) bioreactors have become popular in many industies wih 9

high eta ooding of wastevaer These ote however, afedually belagcvertaken in popula by a novel

‘lot the Iterel Ccalaton 1 bioveattor designed by Paques inthe Netheronds, which has 8

trimer of edrantages coding ete bmecdtezulion ard Liogn aepuaton, geet teres to

ard sera aa ear vale and coneequen on) nde here reactors ces

‘The fist full-scale plant operating a closed Toop system was started up in 1999 ata paper mln

‘Germany t2lpieh Pape Koppa Packaging in the Netherlands has much experience of minimising water consumption for

pspermaking shan centtlized the knowledge gained rom a number ol mils Fagus, th hor as

fellaboratng altady had a lta experience mth paper mil eluents and employed a manager with

Paques poposed new investment tothe Kappa management and also made a proposal fora subsidy

to.a government funding agency, describing the Jango the adventages and the unknowns, The etal

Sicces factor was the manage’ at Pages with pulp and pepe experience Up to 40% of the ost was

Coveted by subsidy nd the detsion to go ahead as made by Kappa onthe bai the ecnoics, ‘closed loop system based on the fist theemophilc IC reactor hat now been commissioned at

!ysten wll establish the advantages of using thermophilic organs ‘he third generation process contemplated forthe paper mls st take the water rom the biologie

tyeatment and use membrane hiation the lant so that dierent qualties can be segmented to specie pars of

Box 9 A paper mill ease study

‘A paper factory, which produces approximately 1 000 tons per day of luting and testliner ithe components of crtagatedcodboaa charges wastewete at 10 ton The average temperature ofthe Tre ater upply i 10°C the elluent emerges at 35°C This iereve Ia temperture resus in an ners los of 1050 ton Overall nergy consumption othe plant lec and seams 730 Mon

“he water re-crultion and parison process (an le bloresctrfllowed by an arabic reaton develops a postive energy balance of 200 Mito les biogas es thus possible to save 250 ton (ie'rfequsalent oa cost reduction of ‘Additionally, the paper mil can now maintain procens water at 35°C with a consequent iaceese of 2% indy paper soli ater pressing The results thatthe speed of the paper machines nreased by 8 with

where a regulatory driver exist (in perhaps three ofthe eases) does the environment become the paramount consideration, for example, the ban on gypsum in the Netherlands or the legal requirement for single enantiomer drugs

‘The case studies cleatly show that systematic strategies ae rarely applied in industy in certo Investigate new biotechnological production pathsiays Rather the Impetus to stat developing biotechnological production processes seems to be a mixture of motivations that vary trom case

to case From the initial conception to the final implementation ofthe scaled-up process, a variety of inhibiting and favouring factors are apparent (apart from the purely technical problems tobe solved)

‘fourth issue, which arses in most of the casestudies s the lack of knowledge of biotechnology,

\shich very often becomes apparent aler the decision for the uptake ofthe new technology has

‘been taken The hard scientists (e chemists grumble that they have to learn the language ofthe biotechnologists, not the other way round This often leads to the need to join forces with external research facilities, such as universities or other companies

a company has knowledge about the technology and the economic (and to a lesser degree the environmental consequences of the technology, the decision process is fairly smooth and the

‘ecsions made are reasonable and timely company that recognises that t does not have this knowledge in-house and makes a conscious decision to acquire it~ through collaboration with

‘other companies or universities can also ease the decision-making process A company, however, {that tes to make decisions about biotechnology while using the paradigm it has always used for Lwaditional processes falls to realise the problems and advantages of biotechnology Consequently, the decision process is slow and tortuous and may even lea to an incorrect solution

‘final poin illustrated by many cases is that although there may be long lead times for the Introduction of a new technology, development times can be reduced considerably in Subsequent cycles For example, the development time scale for the |SI-CPA process was flatvely long but subsequent biotanslormations for chiral molecules have benefited from this, learning experience and the time scale has been reduced dramatically (Case Study 5

Origins of new processes

Companies began to look at biotechnological altematives fora wide variety of reasons Many have realised that this sa technology that must be embraced and are seeking basic expertise particulary in 2% process development by recruiting fom the blottansfoimations science base,

one company had no pilor experience with biocatalytic processes, but its RED group leader had

long-established contacts with an academic who was active inthe area and knew about his research on

enzymes (Case Study 8), The environmental effects of the biocatalytic process were af limited

Importance to the success ofthis project The process did lead to environmental improvements

compared to other production processes for polyester glues, but the main aim was improved product

{quality The sough-ater process improvements went hand in hand with economic benelis suchas cost

reduction and consumer demand for a"aatural” product

Another company began to look at natural products in response to the possibility of an ol shack —

guarding against the threat of energy restrictions to their business (Case Study 10 Yet another believes

Its renewable fuel technology can bring global environmental beneits Case Study 19

One company hada philosophy in place to develop new products and processes with minimum

environmental impact This company devotes considerable attention tothe development of recycling

technologies for lend-use) products (Case Study 3)

Science push was a driving force for Roche to develop a fully biological, one-step process to

‘manufacture riboflavin to replace a largely chemical, multi-step process (Case Study 1) Environmental’

regulatory pressures are another diver, The polluting nature of smelting and the resulting high cost to

construct and operate clean smelters is favouring hydrometallurgical process options for weatment of

bbase metal sulphide concentrates This s particularly the case for treatment of ores containing problem

clement that are difficult to treat by smelting, such as arsenic or bismuth (Case Study 1)

‘As long as metal producers are allowed to “store” polluted gypsum, this is by ar the cheapest

disposal option However inthe light of changing regulations [the Dutch government has prohibited

further storage of residues at the Budel Zink site from july 2000), alternative processes were essential (Case Study 1

The limited availabilty of an essential rw materia, such as clean water, may be sulcient stimulus

(ase Study 11) Where possible, companies use groundwater asthe source of their water supply The

advantages are evident its bacteriologically sale and can be used without further treatment However

teconamic development is leading to increased pressure on the use of groundwater The groundwater has to be withdrawn from greater depth and as groundwater levels decrease, shortages occur and

‘groundwater quality is deteriorating falnty is increasing),

[An iterative process may be required when a company needs information but is only prepared to

spend money at a later stage, Allied Collolds project analysis was not very sophisticated atthe time of

the project development and the problem was to nurture something novel at low levels of expenditure

The work was therefore justiied a year orto at atime (Case Study 7)

‘An important hurdle isthe question of using genetically modified organisms {GMOs) tn a majesty

ofthe cases the degree to which companies have been concerned about thelr use Is closely linked t0

the confidence they have in national and international regulations In Germany fr example, there were

public and legal restraints against use of GMOs and genetic engincering up to 1993 Since then, clear

Fegulations, based largely an harmonised EC guidelines, have been in place for handling of GMOs in

enclosed systems These have been accompanied by reliable and increasingly quick decisions rom the

authorities, within weeks or months, In Case Study I, there was no public discussion of GMOS [although

Information was made available locally - the company held an open day at the plant and had 10000 vistors) although DNA cannot be detected inthe produc, the latter cannot be declared fee of

gene technology (Case Study I

'Where the product is a pharmaceutical, registration requires documentation on the manufacturing

process Consequently, the development of anew process whether its chemical or biological, whether

ituses GMOs or not, requires that the product be reregistered (Case Study 3)

‘Analysis and data gather

LCA has been used in very few cases Is percelved as 100 complicated and as requiring data that

are dificult to obtain Only the largest companies have undertaken an LCA in house (Case Studies |

1g by companies

oy

‘een as a separate target as such but as an integral part of a wider industrial strategy that inludes

‘economic factors such a5 cost reciction

‘Sometimes the benefits were obvious at an ealy stage Although detailed financial analysis came late, it was clear thatthe bloprocess would be safer simpler, more environmentally tiendly, would have lower concentatios of toxic materials, would have no runaway potential and capital expenditure

‘would be much less and hence the economic scale would be lower (Case Study 7,

Laige companies have generally developed thele own techniques for analysing the relative merits

‘of alternative processes, Small companies have in the past tended to rely on the intuition of stall members with long experience in their industry However, they are beginning to see the need for an ceasily applied kt of tools to systematise the information they have and highlight the information they need {A barrier to the development of eco-friendly processes is the lack ofa systematic search for technologies that favour environmental benefits Applying analytical tools that ientily where effort to reduce environment pollution might best be spent and that draw attention fo areas where RED seems promising could lead to new processes that combine eco-endliness and (cost efficiency,

Most inital data gathering was rather haphazard Since there were few sources of external guidance tothe likely success of relevant bioprocesses, the only way to find out was to do the esearch, Most novel processes and products will require some RED

‘The Ciba approach to project analysis isan iterative process, with the result thatthe approval of

‘capital expenditure becomes a much more systematic examination of the economics rather than being based on decisions of very knowledgeable top management Roche, like ather large companies, monitors the straight-line graph of log costs against log

‘cumulative production quantity and requires a new process to achieve respect tobe suecesstul a significant improvement in this

In Avecia, a combined business and technical team uses a technique known as New Opportunities Management Process (NOMP! to respond {0 enquities for new processes or products, The NOMP, process has milestones throughout the development activity and alternatives are all compared against

‘8 checklist onthe basis of timing, cost and quality

‘One company kindly undertook to use the Green Index to compare a new version ofits process to manufacture acrylamide with the earlier catalytic process, and the results {see the annex to Case

‘Study 0} demonstiate the improved environmental friendliness ofthe enzymatic process

Collaboration with university departments is the best way for small companies to meet their information needs However, collaboration is a two-way street and must also be viewed Irom the

‘academics point of view Not only is continuity of RED an important consideration, so also are the funding and the vewards for discovery (Case Stud 8) For example, changes In company structure can be problematic for a university pattner for two reasons Fes, it can make access to the industial research laboratory more dificult, and second, overseas take-overs can reduce the number of potential

‘ovoperation partners in national promotion programmes f patent rights are inadequately secured,

‘cademie researchers may be excluded from future work (Case Study 13)

Decision making and decision makers

Decisions at the stat of any innovative biotechnology project are usually taken by high-level management who need to be aviare ofthe possibilities offered by production-intearated techniques L2 Companies in many sectors that might make use of biotechnology do not do so because they lack this

awareness, Stuctual factors, such asa prevalence of small companies ina glven sector othe lack of

Salfciently detailed data on environmental pestormance, can slow the uptake of biotechnology

‘Questions often raised at an ealy stage include: “Where can we add most value?” and "Where is

the best location to do any development?” In contrast, a comment regularly heard (about

biotechnology! is: “This is not our heritage, not what we know” Such doubts require some very

convincing arguments

CChanges in the marketplace can provide these arguments For instance the pressure exerted on

‘margins for certain antibiotics by companies from Asia and India that focus primarily on market share Ted DSN to develop more efficent technologies The driver for the company to remaln a manufacturer

fof antibiotics in spite of high competition and low margins is the attractive size of the market

{worldwide sales of antibiotics in 1998 amounted to USD 189 billion,

Roche, onthe other hand, did not really need a new process, since they had the necessary capacity

tomect market demand They had therefore to demonstrate that a blopracess had good payback even

when thelr existing chemical plant was closed

Costbeneft analysis is such an integral part of project management that many companies repeat it

at milestones throughout the project development although the costs may be reasonably easily

assessed, benefits may be more dificult to measure, especially ifthe company is unfamiliar with the

required technology A company may not be interested in new processes that improve environmental

Sustainability even though operating costs may be reduced if they have alteady invested in new plant

‘waste minimisation and recycling Appropriate tools are often missing to allow aeliable assessment of

the advantages and disadvantages of the new process The major advantage of bioprocesses, Roche

believes, is that only marginal improvements are possible in well-established and continuously

improved chemical processes, while fermentation has a large scope for increases in prodictiviy

From Lurais experience Case Study 10), the development of anew process has four stages:

+ Tofind a parner to carryout the RED This might be an university a public research institute or another company

+ The RED itselt This step can be subdivided, Alter each milestone a ga/no-go decision is taken Intetnal opposition to Innovation can most elicently be avercome by fats ie by achieving set

‘goals or milestones,

+ The third step, scaling up, is usually done in co-operation with the user company In this case dllfering interests could be a problem as one company (the supplies) s usually interested in

selling the process to a number of companies, whereas the other (the user! would preter to use the technology exclusively,

+ Intioduction of the product/process In this stag, it Is cuca forthe engineering company t0 have demonsteation pilot plantsin operation

Certain considerations make it easier to raise @ budget for RED on a new project These include

short duration from the start of the projec tothe introduction inte the market, low rsh low cost for staff

and equipment and a powerul parer during RED

Some ofthe companies believe that a positive lactor i a personal promoter or champion inside the

company who is dedicated tothe projec and takes the initiative throughout the whole implementation

process This may not be the optimal procedure as a decision on the implementation of new technologies

‘Should be based! on broad consensus among those responsible, rather than depend solely on one person Only ifthe decision to implement a new technology is embodied in the responsible management

sSructre is continuous support guaranteed until the fll scale process is operational,

Projects in Allied Colloids tended to be supported by the enthusiasm of senior executives, many of

\whom were chemists and engineers who had grown up with the company Following the take-over by

Ciba all the senior management were new to the industry on the ather hand, they had a very detailed

system for project analysis (Case Study 7), —