Biotech trendsKarin Hedebo Wassard, NNE Pharmaplan

IndustriFarmaceutForeningen28. September 2011

Dagens menu …..Præsentationen vil fokusere på Biotech og de tendenser vi oplever internationalt, bla. ud fra vores opgaver, forespørgsler, konferencer og arbejde i internationale organisationer som ISPE og PDA.

Blandt disse kan nævnes eksempelvis- brugen af single use materialer i biotech produktion fra råvarertil formulering og fyld- multiprodukt faciliteter- areal optimeringer, samt- modulære faciliteter til såvel produktion som kvalitetstest

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Hvem er I ?

Hvem er jeg ….Karin Hedebo Wassard

Kemi ingeniør 1995Ph.D. 1998EBA

Erfaring inden for:- Forbrænding / bioenergi – det var der jeg startede- Partikel teknologi: udvikling, optimering, nye processer- Men de sidste 10 år inden for pharma/biotech

- Konsulent (NP): 2001-2004 & 2009-…- Som bruger: 2004-2009, Bavarian Nordic, Vaccine- Specialer: Single use processing (biotech)

VaccinerBiocontainment

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Hvor har vi vores input fra ?

We employ close to 1,700 people at more than 25 locations in 11 countries around the world.

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97% of our revenues

come from the pharma and biotech

industries

Our future outlook

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We advise organisations

such asISPE, PDA, ISO, FDA, SFDA, EMA

and WHO

Hvad er det så for trends, som vi ser dem ?

Er det en stor sammensværgelse ?

Det hele hænger jo næsten sammen …

Den enlige svale … ASTM E2500

ASTM E2500 verificationASTM E2500 is referred to as the validation of the future. How much money can it save you?

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Men det er jo ikke kun for Biotech …..

ASTM E2500 verificationSkiftet fra at “gøre som vi plejer” mht. Kvalificering og validering

til i stedet at sikre fokus på det rette, det der virkelig betyder noget i forhold til patientsikkerhed

Mere forhåndsarbejde ved at afklare:- Vi skal vide mere om processerne for at kunne lave de risikovurderinger der skal bruges - Hvad skal testes, hvorfor og hvordan?

=> Anden fokus i kvalitetsarbejdet ……Risikovurderinger bliver en ny hovedopgave, som baggrund for fx bracketing af materialer/test mm.

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Alle de andre:Blockbuster => flere mindre produkter

De nye produkterMultiprodukt / fleksibilitet

Mindre faciliteterSingle use

Fra den enlige blockbuster til de mange produkter

ParadigmShift

Old Pharma New Pharma

Fra store fabrikker til de små fleksible/multiprodukt

ParadigmShift

Old Pharma New Pharma

EquipmentPipingVesselsInstrumentsValvesVeldingsControls…

EquipmentPipingVesselsInstrumentsValvesVeldingsControls…

FlexibilityBags

TubesFittings

Data collectionSupervisionSterilizationContainment

…

Picture: Sartorius/Stedim

Hvad er der i pipelinen ?

PhRMA 2008 Biotech Report, USA VFA 2009 Report, Germany

16Slide from ISPE DACH Marseille SU conference, 2011, Source: Elan

17Slide from ISPE DACH Marseille SU conference, 2011, Source: Elan

Pharmaceutical Product Technology

DiscoverDiscover

Devel

op

Devel

op

Gro

w

Gro

w

Cut costs orSell off

Cut costs orSell offHorizon 1:

Existing products:Mainly Oral Solid Dosage Forms

Horizon 2: The existing NEW products growingon the marketMainly Biopharmaceuticals, Biosimilars, Vaccines and MAbs

Horizon 3: The next generation productsPersonalized Drugs?

20 years of history in Pharmaceutical Product Technology

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22

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SmallMolecules

Biopharma

Personalized

Innovation ChallengeExample: Japan 2009

Norikazu Eiki, Bayer Yakuhin, Ltd.: „Growth Strategy for Pharmaceutical Industry in Japan”

Personalised drugs and treatment

The general trend moves away from ‘blockbuster’ drugs to more personalised drugs, presenting completely new challenges to pharma companies – or hospitals …...

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Vaccine is Prevention of diseases

“While new drugs and vaccines offer progress, psychological and social techniques to improve compliance with existing therapies, and to change human behaviour to aid prevention, are still among the greatest potential benefits in the years ahead.”

Largest Single R&D Segment

US PhRMA 2008 Biotech Report

Cervical Cancer Vaccines

CMO

Pilot Plant

PP->Production

Production 1000L

1000-2000L

250L

250-1000L Multiproduct, high output per process area

Facility Scale Element of Next Generation Mab facility

Away from steel bioreactors, area and cost savings

Multiproduct, flexible facility, biosimilars element

Reality of single useHousekeeping, tracking, operations

1

2

3

4

Next generation MAbs

The big picture: - A new paradigm for MAb bulk production facilities- Massively changed facility design- Cost and timelines reduced significantly

Higher yields Single Use

Nextgeneration

facility

A new 6-pack!

Single Use Traditional

• Yields• Single Use• Process intensification• Volume forecasts

1000 kg Mab/year

Bioreactor volume [liter] 20000 2000Bioreactors 6 6Yield [g/liter] 0,5 5Output [Kg MAb/year] 1013 1013

Batch time [weeks] 2 2DSP yield 75% 75%Production [weeks] 45 45

A new facility design paradigm

Media prep

Upstream

Downstream

Media hold

Harvest

Buffer prep

Buffer farm

Seed train

TraditionalSingle UseSingle Usemixing

Single Usebioreactors

In-linedilution

Single UseHold bags

Single Usefiltration

Single UseSeed train

MembraneChrom

Future: A greener facility• 10X is 10X: Environmental impact improved on kg MAb basis

• Process intensification largest factor in improving green footprint• Water• Energy• Consumables• No. people driving to work

• Single Use direct reductions:• Water, chemicals• Energy – approx. 50%

• SU solid waste:• Landfill leaves little CO2-footprint but is not sustainable• Incineration provides energy recovery

Energy consumption: Comparison of 1000L scale SU and Stainlesssteel process. Rawlings and Pora, Bioprocess International, 2009

• Colder SIP

Today’s alternative to SS systems- Single Use (SU) technology

• Hyclone

Nunc

Millipore

StedimATMI

GE-Wave

Pall Sartorius

Spectrum

• SciCon

Pall

SU tech - applications

• Disposable process, schematic

HYCLONE STEDIMWAVE BIOTECH CENTRITECH TC TECH CELSIUS

• Stainless process, schematic

Bioreactors – Single Use (SU)• Working volumes 50–2000 liters recently available, works fine• Bag: Multilayer film, product contacting layer typical low density PE

polymer• Flexible tubing, pushing liquids around, • Challenges: Agitation, sensors, heat transfer

Sartorius Hyclone ATMI Xcellerex

No. I/O's for SS vs. SU bioreactors

0

20

40

60

80

100

120

140

160

f I/O's 140 41 22 21

Stainless steel Automated

Stainless Steel Low

Automation

Single Use rocker

Single UseBioreactor

Case: SU area and cost impact• Client: Biotech company, new pilot plant

• What’s in the project?• Investigate SU impact on cost and area in MAb upstream processes. • Provide design solutions for process and suite configuration for excisting facility• Media prep, bioreactors, harvest

• Key learnings – single use impact:• 15-20% area reduction• 20-30% cost reduction• Variable cost improved

% area reduction as function of percentage of process modules being single use. Case 1: Stainless steel with a few media bags.

Hvad betyder alt det for os i praksis?

Hvad er effekten af dette?Dels vil ASTM E2500 slå mere igennem, dvs. der vil blive mere fokus på risikovurderinger inden for næsten alt hvad der laves

Fleksibilitet bliver en hoved driver i nye projekter- Og vil understøttes af single use der hvor det giver mening, fx relateret til multiprodukt faciliteter - Undgår vaskevalidering, MEN får extractables/leachables

MEN single use er ikke bare en anden form for reaktor/tank/….udstyrDet er OGSÅ- En helt anden afhængighed af leverandører (2 styk er ikke altid nemt)- En anden indkøbs filosofi / strategi / kontakt- En anden type opgaver i QA – meget mere fokus på audits- Nye typer layouts og flow krav i faciliteter- Lavere klassificeringer ved lukkede processer- Anywhere teknologi – hvor man kan få materialerne

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New Concept for Design of Modern Vaccine FacilitiesFrom made-to-order to made-to-configure.

New Concept - Why do we do it ?

• Global need for more affordable vaccines

• Global focus on domestic supply in emerging countries

• Lack of highly skilled construction people/companies for biocontainment projects in emerging countries

• Lack of trained and skilled operators (training will be required)

• Turn key project model

• Lower the cost for vaccine facilities – with focus on BSL2/3

Objective – project drivers !• Concept for developing a number of standardised process/utility modules that

can be combined in various ways for setting up flexible vaccine facilities mainly in emerging countries.

• High quality at minimal cost

• Comply with GMP – potentially pre-qualified

• Fit to Green Field situation as well as ‘add on’

• Turn key a possibility

• Fast Track

Facility type one: Manufacturing of small scale Inactivated Virus vaccines based on cell culture like Measles, IPV, Rabies, ….

A: Building modules build off site (Pre-fab) – traditional SS solution for equipment

B: Building modules build off site – SU (single use) solution

C: Building on site - traditional SS solution for equipment

D: Building on site – SU solution

SUtechnology

SStechnology

Buildingmodulesoff site

Building‘modules’on site

Option A - design drivers!• Standardisation

• Modular design / Modular Approach

• Manufacturing of modules in low cost countries at high quality (Pre-fab)

• Modular construction

• Turn key project approach

• SU-technology

Xcellerex Hyclone ATMI

Standardisation principles!…combine

• Industry-standard process architecture for:- Bioprocesses and process support- Access airlocks (PAL’s and MAL’s) and corridors

• Modularisation and prefabrication principles.- Modular building blocks for processes and building.- Prefabricated units – assembled, disassembled and

reassembled.

• Flexible configuration.

… for rapid response, cost-effective facilities.

Standard architecture.

Modular & Pre-fab.

Configurable flexibility

Facility standardisation

Industry standard Process architecture

…combines

• Process understanding of industrial vaccine manufacturing.

• Space requirements for different facility biotypes.- Up to 500L bioreactor capacity.- Between 500 – 1000L bioreactor capacity.

• ”Snap-in” modular design for upgrades, addition and expansion.

… for standardisation of process modules.

Process understanding

Space req. for 500 – 1000L

”Snap-in”modules

Process architecture

Modularisation and Pre-fab…combine

• …modularisation of common process denominators supporting the core process.

• …decentralised and parallel production of modules for process operations and construction.

• …pre-fabricated standardised modules, for off-the-shelf process functionalities.

… for rapid response, cost-effective solutions.

Common process denominators

Decentralised production

Off-the-shelf functionalities

Modularisation & Pre-fab

Functions

1

2 3 4 5 6

1. Basic production process structure.2. – 6. Support functions.• Administration, Main gowning, etc.• Receive / Dispatch.• Laboratories.• Utility – black / clean.• Hazardous support

Flexible design for future expansion 3D

Cost impact!• Standardisation• Modular design / Modular Approach• Modular construction• Manufacturing of modules in low cost countries at high quality• Turn key project approach• SU-technology

• Cost reduction of 35-50% relative to a the traditional way of designing by using SS, on site construction and dedicated design

• Project time from start of Basic Design to end of OQ can be done in 12 to 18 month. Typical schedule of today is 36 to 48 month.

SUtechnology

SStechnology

Buildingmodulesoff site

Building‘modules’on site

Acknowledgements

My colleagues at NNE Pharmaplan

• Niels Guldager• Klaus Hermansen• Brian Andersen• Henriette SchubertAnd others• Birgitte Dornonville de la Cour, Bavarian Nordic

Contact details

Karin Hedebo WassardSenior consultant

Specialist biocontainment,vaccines & single use processing

NNE Pharmaplan, Denmarkkhw@nnepharmaplan.com+45 30793996