From cold to hot: Building a modern biobank for a healthy future

Tecan Symposium 2011: Translational Medicine Mark Divers, Karolinska Institute & BBMRI.se Overview • Background: the biobanking challenge • Karolinska Institute Biobank • Creating a large‐scale national facility • The Impact and Value of Biobanks A biobank is like a compound bank! • Huge numbers of diverse samples • Sample quality essential – Physical, scientific relevance, data • Rapid, selective access (cherry‐picking) • Demands automation • Massive informatics opportunities – charting scientific space: chemical or biological • Fabulous asset – To benefit to human health But a biobank is not like a compound bank! • Size – multi‐millions • Extreme storage conditions (complex samples) – Restricts automation • Access and usage – Access and usage technologies still emerging • Ethics – And law • Longer‐term investment – Decades – How do we judge the impact? • Not a well‐established activity at large scale – yet What do you associate with the word biobank? But biobanking is hot!

• Big interest and growing • >>$B spend recent years • Many biobanks in many forms • eg ~900 in • Advanced technologies need the best samples • And many of them • Very big population studies emerging • Hunt, UK Biobank, LifeLines, LifeGene + … • Growing impact on biomedical research

• Huge epidemiology and public health opportunity 6 Yet we must still keep cool!... Quality has been a problem Samples •Collection •Processing •Storage •Data •Access Donors •Selection

•Availability See… Wired May 2010 • Wired May 2010 • Nature July 2011 A brief history of Karolinska Institue Biobank …a research biobank in a medical university

Progressive growth • Huge studies start • Big scale‐up • Capacity • LifeGene pilot • Competence • BBMRI.se • Quality • 1st withdrawals • Study diversity • Quality System and ISO acreditation • Data support to external collections

• Lab, data systems, processes • Ethics and legal compliance addressed • 1st studies, incl. Twingene KI Biobank is home to >70 diverse studies • Disease‐based • Cancer • Neurology • Cardiovascular Ulsam DNA TwinGene • Inflammation TOSS komplettering Tissue Biobank KS Test -studie TCHAD TBI Södertäljehjärtan • Population‐based Stroke STAR STANLEY STAGE-ADHD 120000 STAGE Saliva STAGE SPP-Sthlm SPC SNACK SLE Number of processed samples per study and year SHEEP SCI SCALE SBP 100000 SATSA8 SATSA7 SATSA_twinstudy Sandra CMM SALTY Sahlgrenska Caidahl Rely Rasmusen, Tvillingstudien Rainer CCK PROCAP 80000 Part projekt Parkinson_twinstudy parkinson PAIN Optimization OLIN NOAK Neurotec HS 60000 Molecular medicine, Harvest MIA MEB Employees LUFT Lore LIBRO-1 Lars Lind KTS KTH Kristina Melkersson 40000 KOL IMSE Henrik G Harmony_twinstudy Glaser GEMS Gallsten Första barnet Filterpappersstudien FAST 20000 EXT Eurospan EuroClot Epi Ekonomiskt beteende EIMS-Saliv EIMS DOGSS DNA-kvalitetskontroll 1 Dennis H Astra-Zeneca 0 Delext COSM (Oragene) CEFAM CEFALO 2004 2006 2008 CCK 8 CC10 CATSS CAPSFAM CAPS2 CAPS1 CAPS Broad Bipolära Biobank_intern_1 BIOAIR Beroende >1.5M samples stored, tracked and accessed Basal BAMSE ALfext ALF ALB Genetics AISS Sample statistics 2004-2011

Namn Efternamn 21 februari 2012 10 Typical biobanking studies in research

• 250 – 15.000 individuals • Ca.2 samples / individual • 300 – 400 samples / day • Generate 5‐10 aliquots (0.5‐1ml) / individual • Wide range of logistic demands and solutions • Little automation The large-scale biobanking challenge

Breast Cancer ”Karma” 10/01 • 100.000 individuals

Prostate Cancer ”Stockholm– And‐2” repeat samples to follow • 100.000 individuals• 3 sample tubes / individual22/11 • 3 sample tube /• individual300‐400 individuals / day LifeGene + BBMRI.se • 400‐600 individuals• 16 / dayaliquots (225ul) / individual 01/11 • Scapis • 500.000 individuals • More automated • >16 aliquots (225ul) / individual • Epi Health • And• repeatMore samples automated to• followPilot completing • Malmö Kost – Full‐scale start 1Q2011 • 7 sample• tubesPilot completing / individual Cancer • … – Full‐scale start 23/11/2010 • 100‐200 individuals / day • 48 aliquots (225ul) / individual • More automated • Pilot complete • Full‐scale start 101101 While researchers want much better access to their assets! • Many assets • Long‐term safe storage • With quick reliable access • To exploit diverse analysis opportunities From this… To this… What does this mean?

• >>>30M aliquots to store, track and search

• Massive capacity challenge • Storage • Retrieval • Data management

 Big change… • Create a new large‐scale operation How to take the big leap?

• Automate • Miniaturise • Collaborate • Continuous improvement

 Step‐wise progress built on real needs • Defined sample collections for defined aims Sounds great, but who’s going to support that?...

…And where does the money come from? Introducing BBMRI…

• European initiative started in 2008 by ESFRI* • Create a hub‐and‐spoke network of national competence centres, co‐operating with regional centres

* ESFRI = European Strategy Forum on Research Infrastructures With a grand vision

•Network: connect modern biobanks! •Vision: link 300 biobanks across Europe •Harmonise: evolve common standards! •Avoid re‐inventing wheels!! •New technology •test and apply the best!

• Now >50 members, >30 countries • Applying for tax exemption status • Several national hubs underway: • BBMRI.se, BBMRI.nl, BBMRI.fi, BBMRI.no, BBMRI.it, BBMRI.at • Swedish Science Research Council + KI agreed to fund BBMRI.se • 5 year grant BBMRI.se is a sum of parts to create a unified biobank infrastructure for Sweden Project 1 – management Project 8 Projects 2 & 3 Project 4 Project 5 Project 6 Project 7 Financing Collection: Analysis: IT Physical Ethics Input Output Facility Ensure long‐ Samples & Interface to Unified Unified large‐ Unified term data from analysis national scale sample approach sustainabilit population & resources informatics handling to ethics: y disease platform platform expertise cohorts think‐tank

Common storage and withdrawal -80° C freezers or N2 stores ~100 million tubes = “hard drive” Distributed sample handling at local Automatic repicking unit -20° C biobanks and hospitals Fast withdrawal of tubes = “processor and RAM memory” Where are we now? 2-D coded microtubes are our new currency From this To this

Standard cryo‐tubes Micro‐tubes • manual boxed • 96‐format racks • Conventional barcode • 2‐D barcode • Screw caps • Foil sealed 21 10/10/2010 Mark Divers Large-scale sample input now a reality

22 New DNA banking service is taking shape

• Magnetic bead technology • Early technical problems solved • >20.000 DNA samples so far • Improving processes • 3 systems installed • goal 1000 extracts / day • Stable yield • Avoid normalisation • Good quality 23 Getting samples out: the first step in biobank value

• 1st retrieval in our new systems • 6K DNA samples, breast cancer study • Cancer SNP profile • Prostate cancer retrieval autumn • 2.5K selected DNA samples • Based on PSA values • LifeGene retrieval planned 1Q2012 • Call for research proposals autumn

24 Development continues… 3 critical strategic goals 2011-12

 Retrieval  National network  Enriching the sample collection

25 Automated retrieval: the challenge and the plans… (=how do we help Anna?) ••MultiMulti‐‐millionmillion aliquotsaliquots ••‐‐20,20, ‐ ‐8080 oror ‐ ‐190190°°CC ••InstantInstant accessaccess ••Cost!!Cost!! •Pilot develop with new auto‐picker •Install big DNA auto‐store •‐20°C; 400K samples; ~5MSEK •Plan a multi‐million ‐80°C auto‐store 26 Create a shared BBMRI.se operation We can’t do this alone! Creating BBMRI.se national network

Progressive build up Co‐ordinated: • Göteborg node •Facilities •Equipment & consumables • launch Jan 2012 •IT system •Staffing • 1st project: Scapis •Process • Malmö node • launch 1H2012 • 1st projects: EpiHealth, MKC, MFM • Linköping? • launch 2H2012 • project identified •Others to follow 28 Enriching the BBMRI.se bank 2010-2012 Population cohorts National disease collections •LifeGene (500K) •Multiple Sclerosis •Prostate cancer 2 (100K) + Quality register‐based: •Breast cancer (100K •Rheumatoid Arthritis •Epi Health N (150K) •Bipolar disease •EpiHealth S (150K) • cancers •Scapis CV (30K) •Malmö Diet & Cancer (18K) Emerging pipeline (possibilities): •Malmö Preventative Medicine • North Pop (Norrland) (22K) • IDEFICS (West Sweden) 29 •Prostate cancer 3 (200K) Why are we doing this?...

Study publications …to advance medical research! GALLSTEN 4 PAIN 2 •enable advanced biological analysis BAMSE 8 SCALE 15 •systematic Ekonomiskt beteende 2 •with statistical power TwinGene & Euroclot 13 HARMONY & 12 •Huge potential for public health SATSA KTS 1 •Realise some dreams CAPS 40 Totalt 97 Emerging highlights •Personalised medicine • Multiple Sclerosis •Predictive healthcare • TwinGene • Broad • Influenza Like Illnesses • Prostate Cancer What is the value of biobanking?...

Multiple sclerosis studies give a good example*

• ~17K MS cases in Sweden • Many represented in KI biobank • New therapy, Tysabri™ • Monoclonal antibody • Very effective, very expensive • But critical side effects in some (viral cross‐reacton) • Screen MS biobank for virus • Save big drug cost • Save lives *T Olsson et al • Save lives 31 Several other great examples

• Human Papilloma Virus and cervical cancer • Vaccination scheme • Biobanked serum samples from 1969 (Sigstad et al, Br J Cancer 2002;87:175–180) • Abacavir® anti‐HIV therapy • Identify genetic hypersensitivity sub‐population (Hansson M, Personalized Med,2010;7(1): 75‐85) This is a development!

Still in the early phase! = lärdom

•Technology •Partnerships with researchers •Communication och culture •Collaboration •Evolution not revolution Acknowledgements The BBMRI Crew The Biobank Crew Joakim Dillner Jan-Erik Litton Lab Operations Biobank IT Buisness consultant Mats Hansson Carita Rask Anders Brinne Per Spångeus Göran Hallmans Jaspal Singh Staffan Bergh Ulf Landegren Cecilia Agardh Olle Bäck Biobank Development Joakim Galli Peter Arnerlöv Ulrika Bohlin Gunnel Tybring Lars-Olof Hansson Anci Carman Bengt-Erik Fröberg Joyce Carlsson Pia Hillelson Johan Steninger Lisen Arnheim-Dahlström Camilla Lagerberg Customer Relations Sofie Pettersson Vian Osman Tove Rylander-Rudqvist Martin Fransson Amina Said Scarab IT Cecilia Björkdahl Loreana Norlin Anette Selander Eva Büren* Maria Anderberg Johanna Smith Daniel Ericson Quality Eva Åström José Tapia Anette Petersson Anni Åsberg Mirja Larsson The LifeGene Crew Emma Ridell including William Day Jens Mattsson Valentina Novak Others @ KI Kicki Kjaergaard Henrik Grönberg Mats Thurman Nancy Pedersen Camilla Björk Rune Franson Thomas Bergman Ola Steinberg

More info http://ki.se/kibiobank www.bbmri.se 35 www.lifegene.se That was a quick overview!

Don’t hesitate to make contact for more info!

http://ki.se/kibiobank www.bbmri.se