Pharma på tværs

3. November 2018

Flemming MadsenInstitut for Farmaci

School of Pharmaceutical Sciences (PharmaSchool)

Det Sundhedsvidenskabelige Fakultet

Fremtidens lægemidler Forskning

& Uddannelse

Agenda

• Setting the scene – The transformation – changes and challenges

• What are we doing at the pharmaceutical departments addressing “future medicines” ?

• Shaping the new tomorrow

• Education of future drug experts? What and how?

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Disclaimer for this presentation

• Mainly a UCPH Pharma academic perspective – looking out -> looking in

• Cohesive narrative intended, but it may be a fragmented telling due to the complexity of “the everything” – there will be missing links and blind spots

• No promises made or solutions given on the future medicines

• Most likely more questions than answers

• Maybe you have the answers?

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Let’s get started!The future is waiting

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The future of medicines?Looking out of the window of the

Head of Department office

Our Mission

Pharmaceutical sciences are devoted to tomorrow’s challenge to the development and use of new medicines that can prevent or cure currently incurable diseases. Today’s challenge is to get to tomorrow – and that’s a challenge.

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The world is changing:• Societal, technological and economic drivers

Implications for pharmaceutical/drug sciences?• The pharmaceutical market place and health care are transforming • Universities and academia are going/will go through transformation• Pharmaceutical sciences are in transition – “value chains” are being

redefined

Very little is or will be “business as usual”

Some factors transforming the ”Pharmaceutical Market Place” and Health Care

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The Technological push –Industry 4.0 - BIG DATA ; AI etc..

The empowered patient

Instances of chronic disease are increasing -> stretched healthcare budgets

Healthcare policy-makers and payers are increasingly mandating what doctors can prescribe

A growing number of healthcare payers are measuring the pharmaco-economic performance of different medicines. A widespread use of electronic medical records will give them the data they need to insist on outcomes-based pricing

Boundaries between different forms of healthcare are blurring, as clinical advances render previously fatal diseases chronic and the self-medication sector expands

Demand for medicines is growing more rapidly in the emerging economies than the industrialized economies

Governments are beginning to focus on prevention rather than treatment, but not yet invested very much in pre-emptive measures;

Regulatory dilemmas:• challenge in approval of truly

innovative medicines and treatments (who and how),

• fast-tracks for approval• Individualized/stratified

medicines

Pharmacy practice• A change in practice? • Towards person-oriented

health-care and changing distribution chains?

Demographics

Some factors transforming the ”Pharmaceutical Market Place” and Health Care - industry challenges

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Low scientific productivityPharma’s output has remained at a stable level for the past decade. Using the same discovering and developing processes, there’s little reason to think its productivity will suddenly soar. Industry is rethinking R&D structures including different collaborative models – Biotech companies pushes boundaries

Rising customer expectationsThe commercial environment is getting harsher, as healthcare payers impose new cost constraints on healthcare providers and scrutinize the value medicines offer much more carefully. They want new therapies that are clinically and economically better than the existing alternatives, together with hard, real-world outcomes data to back any claims about a medicine’s superiority. Patient empowerment adds to.

Cultural sclerosisFor many years, the prevailing management culture, mental models and strategies on which the industry relies have been rooted in a ´traditional’ business model, on, even though they’ve been eclipsed by new ways of doing business. However, a huge transformation towards more collaborative engagements and different value propositions are on-going

Pharmaceutical Sciences – translating transforming factors into scientific challenges

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Drug design and discoveryThe need for new drugs to combat diseases with major impact on health and economics

• New anti-infective drugs• New drugs for treatment of diseases

of CNS disordersDrug discovery based on new mechanism of action

• Selective agonists at (oligomeric) G-protein-coupled receptors

• Epigenetic inhibitors• Protein-protein interactions as drug

targets• The application of systems biology

and organ- and body-on-a-chip• Increased use of human tissue (stem

cells)Process chemistry (including a “green chemistry” approach)

• Synthesis of oligosaccharides as building blocks for anti-body drug conjugates

• Flow reactor systems (microreactors)• Genotoxic impurities

AI/Machine learning and drug discovery

Formulation design and pharmaceutical technology• Continuous manufacture• Non-parenteral

formulations of macromolecules

• Commercial manufacturing of nanoscale drug delivery systems

• Formulations on demand• Novel excipients

And the rest of it:• Social and behavorial sciences (medicines use); • Pharmacoeconomics• Pharmacovigilance (pharmacoepidemiological studies and drug safety

surveillance)

Translational research and individualized medicines• The clinical value of genetic testing• The role of bioinformatics and “Big Data”• Ethical, legal and social implications of

individualized or stratified medicine• The application of pharmacogenetics in

drug development• Educational barriers (coordinated

education and training of all health care professionals)

Biotechnology• New

therapeutic advances

• Process, manufacturing and impurities

• Comparability and biosimilars

• Administration devices

Analytical sciences and quality• High-throughput

screening• New analytical methods• Imaging• Biomarkers• Biosimilars• International

harmonization of bioanalytical guidance

• Diagnostics and quality medicines

Pharmacokinetics, pharmacodynamics and system biology (drug metabolism)• Physiologically based

pharmacokinetic modelling

• System pharmacology model

• Qualification of PBPK and systems models

Global Health CommentaryCurrent Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective; Tucker G. et al., Journal of Pharmaceutical Sciences, vol. 105 (9), Sep. 2016, p.2489-2497

Regulatory sciences• Biopharmaceutical classification schemes• Advanced therapeutics• Bioequivalence• International harmonization of bridging

studies and the design of global clinical trials• International harmonization of biosimilar

versions of biologics

The University Transformation

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Life at the university

“In this country, you see, it takes all the running you can do, to keep in the same place”

“If you want to get somewhere else, you must run twice as fast as that”

The Red Queen citations (Lewis Carroll, Through the Looking Glass, and what Alice found there, Macmillan & Co, 1872)

The University transformation (on-going)

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Escaping the Red Queen Effect– re-thinking the university in the new economics of higher education; PA Consulting Report (2009)

Seismic shifts in policy, markets and technology are driving fundamental changes in the environment and economics of higher education

Higher education institutions must undertake a fundamental rethinking of their assumptions on current university business models to match the changed economics of higher education

Fundamental transformation an ‘old world’ of public funding entitlements to a still-forming ‘new world’ of income earned through additional channels and value/impact delivered to client groups/stakeholders (not enough to just meet grant conditions)

Universities must develop new ways of realizing the five essential attributes of successful 21st century universities:

• focus• excellence• agility • impacts• viability

Collaboration and partnerships: Knowledge Transfer Partnerships, Lifelong Learning Networks, franchised courses and services, comer-cializationventures, partnership with domestic and overseas institutions, corporate and government contracts, etc.

The Transformation

What are we doing at the pharmaceutical departments at UCPH addressing “future medicines” ?

When all this is happening as we speak?

(Next slides courtesy CEO, Thomas Senderovitz, Danish Medicines Agency)

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12

• Small molecules

and antibodies

• Treatment of

diseases

• Advanced therapies

• Early intervention

• Biosystem Modification

From To

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• One size fits all • Precision Medicine

From To

© Thomas Senderovitz 2017

7. DECEMBER 201814

•Advanced Therapy

Medicinal Products

• Gene therapy

• Tissue engineering

• Cell therapy

© Thomas Senderovitz 2017

15

•Medical devices –

3D print and beyond

•Augmented / Virtual reality

•Robotics

•Nanotech

16

• Tricorders

• Wearables / nanosensors

• Mobile health / health apps

17

7. DECEMBER 201818

• Connected health

19

• Telemedicine

• Homecare

• Patient as a consumer

20

Big Data

• Big challenges• Big opportunities• Advanced Analytics

• Real time knowledge – real time regulation?

• Real world data – multiple sources – data integrity and validity

Convergence of technologies

Our strategy at Pharma-UPCH

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UPCH strategy objectives

• Excellent basic research and education

• Collaboration and partnership

• Interdisciplinarity

• Internationalisation

• Innovation through excellent basic research and collaboration and partnership

Collaboration in pharmaceutical sciences

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We are in a good (hot)spot!

To:

• Deal with the convergence of health and technology

• Further integrate pharmaceutical sciences with bioengineering, control engineering, information (computational) sciences, behavioral sciences and law.

• Utilize the trinity of knowledge between academia, authorities, and industry from idea to implementation from molecule to society

Who and what for a given collaboration is often the easier part – How to collaborate is the difficult part (barriers and boundaries)!

Pharmaceutical Sciences – translating transforming factors into scientific challenges

07/12/2018 24

Drug design and discoveryThe need for new drugs to combat diseases with major impact on health and economics

• New anti-infective drugs• New drugs for treatment of diseases

of CNS disordersDrug discovery based on new mechanism of action

• Selective agonists at (oligomeric) G-protein-coupled receptors

• Epigenetic inhibitors• Protein-protein interactions as drug

targets• The application of systems biology

and organ- and body-on-a-chip• Increased use of human tissue (stem

cells)Process chemistry (including a “green chemistry” approach)

• Synthesis of oligosaccharides as building blocks for anti-body drug conjugates

• Flow reactor systems (microreactors)• Genotoxic impurities

AI/Machine learning and drug discovery

Formulation design and pharmaceutical technology• Continuous manufacture• Non-parenteral

formulations of macromolecules

• Commercial manufacturing of nanoscale drug delivery systems

• Formulations on demand• Novel excipients

And the rest of it:• Social and behavorial sciences (medicines use); • Pharmacoeconomics• Pharmacovigilance (pharmacoepidemiological studies and drug safety

surveillance)

Translational research and individualized medicines• The clinical value of genetic testing• The role of bioinformatics and “Big Data”• Ethical, legal and social implications of

individualized or stratified medicine• The application of pharmacogenetics in

drug development• Educational barriers (coordinated

education and training of all health care professionals)

Biotechnology• New

therapeutic advances

• Process, manufacturing and impurities

• Comparability and biosimilars

• Administration devices

Analytical sciences and quality• High-throughput

screening• New analytical methods• Imaging• Biomarkers• Biosimilars• International

harmonization of bioanalytical guidance

• Diagnostics and quality medicines

Pharmacokinetics, pharmacodynamics and system biology (drug metabolism)• Physiologically based

pharmacokinetic modelling

• System pharmacology model

• Qualification of PBPK and systems models

Global Health CommentaryCurrent Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective; Tucker G. et al., Journal of Pharmaceutical Sciences, vol. 105 (9), Sep. 2016, p.2489-2497

Regulatory sciences• Biopharmaceutical classification schemes• Advanced therapeutics• Bioequivalence• International harmonization of bridging

studies and the design of global clinical trials• International harmonization of biosimilar

versions of biologics

Tekst starter uden

dato og ”Enhedens

U N I V E R S I T Y O F C O P E N H A G E N Department of PharmacyU N I V E R S I T Y O F C O P E N H A G E N D E P A R T M E N T O F P H A R M A C Y

Drugs – From Molecule to Society

Department of Pharmacy• Basic studies of separation techniques (hyphenated techniques) • Drug metabolism and bioanalysis• Metabonomics and diagnostics.• Qualitative (structural) and quantitative analysis of biopharmaceuticals• Microfluidics and lab-on-chip• Toxicology: Emission, processing and effect of drugs in environments

• Solid state of drugs and dosage forms• Poor soluble drugs• Nanoparticulate systems• Rational oral drug delivery• Drug transporters in ADME• Pharmaceutical physical chemistry

• Biomacromolecular drug delivery and biophysics (formulation and stability of peptides and proteins and siRNA, f.ex. fibrillation)

• Drug delivery of biopharmaceuticals and biological barriers• Vaccines – formulation• Nano Drug Delivery• Imaging: Radioimaging: SPECT, PECT, CT; MRI, Optical imaging

• Pharmaceutical materials science: Molecular-based formulation of solid-state pharmaceutics.

• Process Analytical Techniques (PAT)• Quality by design (QbD)• Continuous manufacturing of personalized medicines

• Pharmacy practice• Pharmacovigilance• Pharmacoepidemiology and drug safety• Clinical Pharmacy• Regulatory Science

PharmacologyBiologyBiostructural

chemistry/

Biopharmaceuticals

Medicinal

ChemistryPharmacotherapy

&

Pharmacovigilance

Molecular

and Cellular

Pharmacology

Natural

Products

and Peptides

Biopharma-

ceuticals

Experimental

Pharmacology

Medicinal

Chemistry

Research

Bio-

structural

Research

Pharmaco-

therapy

Drugs – From Molecule to SocietyDepartment of Drug Design and Pharmacology

Manufacturing and materials

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• Quality by Design (QbD) in nanomedicine context

• Innovative technologies - continuously operating miniaturized production systems- digital design of pharmaceutical products- artificial intelligence (AI) in product design

Prof. Jukka Rantanen

Edible QR codes could be the medicine of tomorrow

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The researchers used the antipsychotic drug haloperidol, dissolved in lactic acid and ethanol, printed on a white substrate

Data like the dose, the patient's name, use by date, manufacturer info, and instructions on how to take the medicine could all appear on a smartphone screen when scanning the medicine

Scan before eating: could edible QR codes be the medicine of tomorrow?

QR encoded smart oral dosage forms by inkjet printingMagnus Edinger, Daniel Bar-Shalom, Niklas Sandler, Jukka Rantanen, Natalja GeninaInternational Journal of Pharmaceutics, Volume 536, Issue 1, 30 January 2018, Pages 138-145

FUTURE DRIVERS –patient-oriented products – different value proposition

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Rantanen, Khinast, 2015. The future of pharmaceutical manufacturing sciences. J.Pharm.Sci. 104 3612–3638.

PATIENT

PHARMACY

PORTABLE DEVICEWireless/mobile wearables, IT

PERSONALIZED MEDICINAL PRODUCT

Flexible dose, novel drug delivery system, combination medication

MANUFACTURING-ON-DEMAND

Flexible, continuously operating, manufacturing lines with real time release

Genomics, diagnostics, miniaturized analytics

Related featuresInformation/material flow

MD

DA

TAB

ASE

Tekst starter uden

dato og ”Enhedens

Copenhagen Centre for Regulatory Science (CORS)

Dias 30

VisionThe Copenhagen Centre for Regulatory Science (CORS) aims at being the international partner for academic leadership in regulatory science, research and education and to participate in building the regulatory framework that will make innovative medicinal products available to patients.

MissionThe Copenhagen Centre for Regulatory Science is a powerful Centre for Regulatory Science influencing and conducting regulatory research and education in an international perspective. The research and education of the Centre makes a clear mark on regulatory decision-making - to the benefit of stakeholders such as patients, authorities, payers and industry

Tekst starter uden

dato og ”Enhedens

Copenhagen Centre for Regulatory Science (CORS)

A holistic approach to regulatory science

Combine internal multidisciplinary strengths of the University and external industry partners and authorities

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Authorities

Industry

Tekst starter uden

dato og ”Enhedens

Copenhagen Centre for Regulatory Science (CORS)

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Partners

University of Copenhagen

Faculty of Health and Medical Sciences:Dept. of PharmacyDept. of Drug Design and PharmacologyDept. of Clinical MedicineDept. of Public HealthBiopeople

Faculty of Law:Centre for Information and Innovation Law

Faculty of Humanities:Dept. of Media, Cognition and Communication

Faculty of Social SciencesCentre for Health Economics and Policy (CHEP)

Authorities

Danish Medicines Agency

Industry

Pharmaceutical CompaniesNovo Nordisk A/SH. Lundbeck A/SFerring PharmaceuticalsLEO Pharma A/S

AI in Drug Discovery

Computational Receptor Biology

PI: David Gloriam

Web: gloriamgroup.org

Computational Drug Design

Multi-million compound databases

Structural bioinformatics

Cheminformatics

GPCRdb database

Integrated data

2,500 users/mo.

Research tools

ResearchData

Methods

Data science

Genetic variants

Machine learning

Statistical regression

Munk et al., Online resource for GPCR crystallography and cryo-EM, Nature Methods, Accepted

Hauser et al., Trends in GPCR drug discovery: new agents, targets …, Nature Reviews Drug Discovery , 2017

Hauser et al., Pharmacogenomics of GPCR drug targets, Cell, 2018

Flock et al., Selectivity determinants of GPCR-G protein binding, Nature, 2017

Xiong et al., Total synthesis and structure-activity relationship studies of …, Nature Chemistry, 2016

5 PublicationsSenior-authored

Co-authored

Cluster: 360+ cores & 13 GPUs (@ SUND-IT)Infrastructure Software: SOA licences 13,000 USD/year

Data science in Pharmacovigilance Research

Expertise

• Pharmacoepidemiological studies and drug safety surveillance using big healthcare data (population-based registers)

• International multi-database network studies

Interdisciplinarity/collaborations

• Strong network at UCPH (Pharmacoepidemiology Research Collaboration) and internationally (NorPEN, ENCePP, Karolinska Institutet, Utrecht University)

Computational infrastructure

• Servers at Statistics Denmark and the Danish Health data authority

PI: Morten Andersen

BIG HEALTHCARE DATA

NORDIC COMMON DATA MODELFOR MULTI-DATABASE NETWORK STUDIES

Selected publicationsBazelier et al. Data management and data analysis techniques in pharmacoepidemiological studies using a pre-planned multi-database approach... Pharmacoepidemiol Drug Saf (PDS), 2015Selmer R et al. Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes... PDS, 2016 But A et al. Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country study. Diabetologia, 2017Pazzagli L et al. Methods for time-varying exposure related problems in pharmacoepidemiology... PDS, 2018Forslund et al. Stroke and bleeding with NOAC or warfarin treatment in patients with NVAF... Europace, 2018

Shaping the new tomorrow’s education

We are putting real-life data into the development of new drugs.

• How do we put real life development into development of our educations?

• We do as good as we can – and we try to adapt (listen, learn and adapt)

• However, science/research moves at one pace (fast) and education at another pace (slower)

• How do we get more proactive rather than reactive?

• Questions to ask? – Things to do?

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Shaping the new tomorrow’s education

The future of pharmaceutical sciences is the next generation of drug experts - the pharmaceutical scientists and candidates

They must:

• Be able to deal with ambiguity and be collaborative, entrepreneurial, and adaptive in their approaches

• Have a strong professional “core”, but also be encoded to work with the perspective that the next scientific breakthrough will be through interdisciplinary collaboration!

• Learn and mentored to build their own public and private networks and partnerships

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Shaping the new tomorrow’s education

FARMA2020: The new curriculum

• Strong unit base (Bachelor) – Varied Master opportunities

• First candidate in 2020 – but perhaps already time to revisit content

• Flexible skeleton – allowing for (semi-)quick changes

• We need to the get the latest research and developments faster to the students!! – They should take part in the research, development and innovation (or at least be more introduced to it)

• We cannot put everything in – something has to go out

Life-long learning is a prerequisite to survive in the future!!

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Shaping the new tomorrowThe future medicines

COLLABORATION

COLLABORATION

COLLABORATIONWithin – Across – Beyond

organisations, disciplines, sectors and borders and with patients

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The future is hereOnce science fiction – now a kind of reality

Star Trek : A tricorder is a multifunction hand-held device used for sensor (environment) scanning, recording data and data analysis (TRI-function reCORDER, referring to the device's primary functions: sensing, computing, and recording).

The standard tricorder is a general-purpose device used primarily to scout unfamiliar areas, make detailed examination of living things, and record and review technical data. The medical tricorder is used by doctors to help diagnose diseases and collect bodily information about a patient (various species and life forms) ; the key difference between this and a standard tricorder is a detachable hand-held high-resolution scanner stored in a compartment of the tricorder when not in use

THANK YOU!

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