The future in drug development. Today. - adrnordest.roadrnordest.ro/user/file/news/16/prezentari_06_06_2016/WG 1... · 1973 - Laboratorul Central de Enzimologie şiFarmacologie Biochimică

The future in drug development. Today.

Assoc. Prof. Bogdan IonelTamba, M.D., PhD.

Centre for the Study and Therapy of Pain

CEMEX, UMF Gr.T. Popa, Iasi, Romania

Iasi, 2016

Traditions…

Our traditions… 1973 - Laboratorul Central de Enzimologie şi Farmacologie Biochimică

1986 - Laboratorul Central de Testare a Medicamentului (peste 100 contracte cercetare medicament)

2001 - Centrul de Studiu şi Terapie a Durerii (singurul din Romania)

2005 - Centrul de excelenţă pentru cercetări fiziofarmacologice celulare şi integrative (unul din cele 2 in UMF)

2006 - Platforma interdisciplinara de formare si cercetare “Platforma de cercetari fiziofarmacologice si clinice asupra mecanismelor durerii

nononcologice si oncologice” 1 milion Euro!

2007-2015 – granturi FP7, ERA-NET, Idei, Parteneriate, POSDRU, etc.

2016 – $10 mil CEMEX – cel mai modern laborator de studii preclinice din EstulEuropei.

Centrul de Studiu si Terapie a Durerii

Tamba B, Iasi, 2016

SECTIUNEA A: DIDACTIC

Our lab before…

Our lab after.

Un scurt reminder….

Obiective 2011

extinderea infrastructurii (echipamente si spatii dedicate)existente ale CSTD si Department of Pain, pentruindeplinirea obiectivelor strategice de cercetareenuntate in continuare.

Tamba B, Iasi, 2016

Tamba B, Iasi, 2016

Obiective 2011

Extinderea infrastructurii(echipamente si spatii dedicate) Granturi nationale depuse in ultimul an:

Experimental Studies on the Relation Between Mitochondrial Dysfunction and Pain; New Perspectives In Pain Therapy – CNCSIS Cercetare Exploratorie 2011

Study on Potential Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation on Different Types of Multiple Sclerosis Clinical Syndromes - CNCSIS Cercetare Exploratorie 2011

Mechanisms of obesity-induced renal injury - CNCSIS Cercetare Exploratorie2011

Innovative design and biological evaluation of new antidiabetic agents as incretin modulators - CNCSIS Cercetare Exploratorie 2011

Cardiovascular dynamics in obesity-induced renal disease - CNCSIS Cercetare Complexa Exploratorie 2011

Tamba B, Iasi, 2016

Obiective 2011

Extinderea infrastructurii(echipamente si spatii dedicate) Granturi europene/internationale depuse in ultimul an:

Helicobacter pylori infection and micronutrient status in population with traditional rural life style and eco diet comparing with urban population with western life style – IAEA 2011

Chemo-hyperthermal Delivery - Combined chemo-hyperthermal control of hepatic tumors, based on microwave-activated subendothelial-targeted nano-assemblies - ERA-Net EuroNanoMed JTC-3 (2011)

Ketamine as an adjuvant to opioids for cancer pain – IASP 2011

Tamba B, Iasi, 2016

Obiective 2011

Extinderea infrastructurii(echipamente si spatii dedicate)

Granturi castigate in ultimul an FP7 AMI4EUROPE - Advanced, Cross-Disciplinary & Integrated Medical

Imaging for all Europeans through a Network of Regional Clusters and Development Strategies, valoarea totala 3.225.844€, (2010-2013).

IASP initiative for improving education, 1 an (2010-2011), 6230 USD

MANUNET ERA NET "Dezvoltarea de bio- senzori prin intermediul uneitehnologii inovative de electroacoperire a structurilor carbonice cu polimeri activi” (CarBioSense) - (2011 - 2013)

Tamba B, Iasi, 2016

Obiective 2011


cointeresarea potentialilor parteneride cercetare sau industriali din tara.

Tamba B, Iasi, 2016

Obiective 2011


cointeresarea potentialilor parteneri decercetare sau industriali din strainatate

Korea Institute of Radiological and Medical Sciences

Tamba B, Iasi, 2016

Obiective 2011

Parteneriate incheiate

Korea Institute of Radiological and Medical Sciences

Tamba B, Iasi, 2016

SECŢIUNEA B: CERCETARE

Termen scurt - mediu 2-3 ani

ma voi implica in activitatile structurilor de finantare sigestionare a cercetarii din Romania si Europa

Tamba B, Iasi, 2016


Ariile tematice de cercetare

Aria de cercetare fundamentala a medicamentului: arii de studiude la descoperirea de noi molecule tinta pana la apreciereautilizarii unui medicament la nivel de animal de laborator

Aria de cercetare preclinica a agentilor terapeutici farmacologici

Aria de Imagistica medicala avansata: utilizarea de tehnici de imagistica medicala de in cercetarea de baza, utilizand animaleca si modele exploreaza procesele fiziologice sau patologice, explorarea farmacogenetica sau a mecanismelor de actiune de

molecule noi; dezvoltarea de produse noi (substante de contrast, radiomarkeri,

imunomarkeri) care sa fie transferate in industrie

Tamba B, Iasi, 2016


Directii de cercetare:

identificarea mecanismelor moleculare si fizio-farmacologice integrative ale substantelor cu actiune medicamentoasa.

bioanaliza si metabolism al medicamentului incluzand determinaribiochimice si imunologice, cromatografie, spectrometrie de masa.

farmacocinetica si farmacodinamie asupra substantelor medicamentoase, care investigheaza atat miscarea agentilor terapeutici prin organism (absorbtia, distributia, metabolizarea si eliminarea) cat si interactiunile siefectele asupra tesuturilor vii.

utilizarea datelor de genomica, inclusiv variabilitatea, diferentele de expresie a ARN si proteinele, pentru a previziona inocuitatea si/saueficacitatea unui medicament administrat la un anumit animal sau grupde animale.

mecanismele moleculare si integrative ale nociceptiei periferice sicentrale.

Tamba B, Iasi, 2016


http://wisdomquarterly.blogspot.com/2008/07/painful-facts-dukkha.html

Directii de cercetare - durerea

Tamba B, Iasi, 2016


http://wisdomquarterly.blogspot.com/2008/07/painful-facts-dukkha.html

Directii de cercetare:

rolul oligolementelor in modularea durerii

dezvoltarea de noi analgezice, coanalgezice sau paranalgezice

toxicologie si teratologie pentru medicamente, dispozitivemedicale si biotehnologii dezvoltate in domeniul produselorfarmaceutice, teste combinate de medicamente si genetica

Dezvoltarea de protocoale pentru introducerea in procesuldidactic a unor tehnici alternative si reutilizarii animalelor

cercetari de nanotehnologie / Sisteme de livrare avansate, cu utilizarea imagisticii medicale avansate de tip PET/RMN.

Studii in vivo, de tip PET/RMN, al celulelor tumorale la animal, cu sau fara interventie farmacologicaTamba B, Iasi, 2016


Directii de cercetare: Dezvoltarea de protocoale pentru introducerea in procesul

didactic a unor tehnici alternative si reutilizarii animalelor

Cercetari de nanotehnologie

Biomarkeri; Substante de contrast

Investigarea modului in care substantele antinociceptive sau unelemetode nonfarmacologice influenteaza mecanismele molecularesi integrative ale nociceptiei periferice si centrale

Eßlucidarea problematicii legata de bolile cardiovasculare, bolineurologice, diabet sau oncologie.

Identificarea si studierea unor noi markeri de boala

unitatea de chirurgie experimentala, care va permite cercetareasi fundamentarea de noi tehnici chirurugicale. Tamba B, Iasi, 2016


Size DOES matter!

A Virus 100 nmBacteria 1 000 nm

Amoeba 10 000 nmPollen grain 100 000 nm

Nematodes 1 000 000 nmInsects 10 000 000 nm

Small mammals 100 000 000 nmLarge mammals 1 000 000 000 nm

Molecules 1 nmDNA 10 nm

Tamba B, Iasi, 2016


Nanotechnology Applications

Information Technology Energy

Medicine Consumer Goods

• Smaller, faster, more energy efficient and powerful computing and other IT-based systems

• More efficient and cost effective technologies for energy production− Solar cells− Fuel cells− Batteries− Bio fuels

• Foods and beverages−Advanced packaging materials,

sensors, and lab-on-chips for food quality testing

• Appliances and textiles−Stain proof, water proof and

wrinkle free textiles• Household and cosmetics

− Self-cleaning and scratch free products, paints, and better cosmetics

• Cancer treatment• Bone treatment• Drug delivery• Appetite control• Drug development• Medical tools• Diagnostic tests• Imaging

Aplicatii ale nanotechnologiilor

Tamba B, Iasi, 2016


24

Beneficii potentiale ale nanotechnologiilor in Drug Delivery

Proprietati îmbunatatite: Solubilitate rata de dizolvare biodisponibilitatea orala capacitatea de tintire

Imbunatatirea dozelor Doze mai mici Profil de efecte secundare mai bun Forme de dozare mai convenabile

Tamba B, Iasi, 2016


NanomedicinaA. Interest in the area has grown exponentially B. Drug delivery is the most productive area

C. Drug delivery is the most established technology in the nanomedicine market

Nature Biotechnology 2006, Vol. 4, pp.1212-1217Tamba B, Iasi, 2016


Cho K et al. (2008) Clin Cancer Res

TIPURI DE NANOPARTICOLE –SISTEME DE LIVRARE

Size range: 1nm to 200 nm.

Tamba B, Iasi, 2016


Drug Delivery

1

3

2

4

1) A nanoparticle carries the pharmaceuticalagent inside its core, while its shell isfunctionalized with a ‘binding’ agent

2) Through the ‘binding’ agent, the ‘targeted’nanoparticle recognizes the target cell. Thefunctionalized nanoparticle shell interactswith the cell membrane

3) The nanoparticle is ingested inside the cell,and interacts with the biomolecules insidethe cell

4) The nanoparticle particles breaks, and thepharmaceutical agent is released

Source: Comprehensive Cancer Center Ohio University

A. Because of their small sizes, nanoparticles are taken by cellswhere large particles would be excluded or cleared from the body

Tamba B, Iasi, 2016


A Drug Delivery NanoparticleA. Nanoparticles for drug delivery can be metal-, polymer-, or lipid-based. Below (left) anexample of the latter, containing SiRNA encapsulated, and functionalized with an specificantibody. SiRNA can control often lethal inflammatory body responses, as shown in themicroscopic images below (right)

Science 2008, Vol. 316, pp 627-630

antibodylipid

SiRNA Healthy tissue Sick tissue treated with non-targeted nanoparticles

Sick tissue treated with targeted nanoparticles

B. C.

Tamba B, Iasi, 2016


A Targeted Polymer NanoparticleA. A dual Nanoparticle, the targetingligand allow it to diagnose if a cell ishealthy or sick, and bind specificallyto the tumorous cell

B. Once inside the cell, thepolymeric nanoparticle degradesand the anticancer agent is set free

C.An imaging agent can be added as wellImaging

agent

Annu. Rev. Biomed. Eng. 2007. Vol. 9, pp. 257–88Tamba B, Iasi, 2016


Targeting QD’s for intracellular imaging

Ligand coated QDNC

QD release

Ingestion

Decomposition

labeling

Nano Letters 2008., Vol. 8, pp3887-3892

A. Using a drug-delivery-like mechanism, a targeted lipid-based nanoparticle (TNP) encapsulatingQD’s specifically ‘attacks’ a cell having the receptors that pair with its ligand coating. Uponingestion and destruction of the TNP, the QD’s are set free and accumulate on intracellularstructures

C. QD (red)intracellular uptake is enhancedwhen using the QDNC instead of the free QD’s

B.

D. Imaging of nucleus (blue) and cytoplasm (other) after 30 min (left) and 3 hours after uptake

Tamba B, Iasi, 2016


Nanotechnology in Health Care

Thermal ablation of cancer cells assisted by nanoshells coated with metallic layer and an external energy source – National Cancer Institute

− Nanoshells have metallic outer layer and silica core

− Selectively attracted to cancer shells either through a phenomena called enhanced permeation retention or due to some molecules coated on the shells

− The nanoshells are heated with an external energy source killing the cancer cells

Thermal ablation of cancer cells

Tamba B, Iasi, 2016


QD Localization of a TumorA. It is possible to overlap X-ray images with infrared images to localize a tumor. The X-rayimages give the images an anatomical context, while the infrared images detect the QD’semission, which correlates to the tumor location (see B.)

Annu. Rev. Biomed. Eng. 2007. Vol. 9, pp. 257–288

B. C. 560-QD-Streptadivin targets and imagesIn-vitro breast cancer cells having the IgGfactor characteristic of chemotherapyresponsive cells

Nature Biotechnology 2003. Vol. 9, pp. 41-46Tamba B, Iasi, 2016


Gold Nanoparticle Tumor DetectionA. The common strategy to detect the tumor is the functionalization of thenanoparticle with an antibody specific to the tumor antigens, and then detectthe nanoparticle by some spectroscopic technique

B. Tumor photograph

Imaging with gold nanoparticles as contrast agent

Nanotechnology 2009. Vol. 20, 395102Tamba B, Iasi, 2016


Target Molecule

1. Chen, G.Y., Thundat, T. Wachter, E. A., Warmack, R. A., “Adsorption-induced surface stress and its effects on resonance frequency of microcantilevers,” J. Appl. Phys 77, pp. 3618-3622 (1995).

2. Ratierri, R. et al., “Sensing of biological substances based on the bending of microfabricated cantilevers,” Sensors and Actuators B 61, 213-217 (1999).

3. Fritz, J. et al. “Translating Biomolecular Recognition into Nanomechanics,” Science 288, 316-318 (2000).

4. Wu, G. et al. “Origin of nanomechanical cantilever motion generated from biomolecular interactions,”PNAS 98(4), 1560-1564 (2001).

Courtesy: Prof. A. Majumdar, U.C. Berkeley

Terapie

A. There is a search dual-mode nanoparticle that can detect a tumor (imaging)and destroy it (therapy)

B. There is two action modes for therapeutical nanoparticles

Passive Targeting Active Targeting

Based on nanoparticle functionalization for specific targeting of cancerous cells

Based on retention effect of particle of certain hydrodynamic

size in cancerous tissues

Tamba B, Iasi, 2016


CEMEX – $10 mil. state of the art R&D facility

Infrastructura de cercetare-dezvoltare complexa,

Echipamente inalt tehnologice

Competitiv pe plan international

Domeniul biomedical, al cercetarilor stiintifice fundamentale si aplicative pe animale de laborator

CEMEX este un proiect co-finanţat prin Fondul European de Dezvoltare Regională, axa prioritară 2 ”Competitivitate prin cercetare, dezvoltare tehnologică şi inovare”, operaţiunea 2.2.1 – “Dezvoltarea infrastructurii de CD existente şi crearea de noi infrastructuri”, în baza contractului de finanţare nr. 635/12.03.2014, cod SMIS-CSNR 48880, director grant Daniela Drugus


Standarde de calitate in cercetare

Obtinerea certificatelor de acreditare de tip ISO si GLPsunt pasi necesari care vor asigura recunoasterea la nivelinternational a cercetarilor efectuate in laborator si vorpermite oferirea de servicii de cercetare fundamentalacatre terte companii sau institutii.

Tamba B, Iasi, 2016


Unitatea Studii Integrative in-vivo

Zona carantina si gazduire

Zona proceduri experimentale (telemetrie) - achizitiacontinua, la distanta, de semnale biologice in vivo, petermen lung, in animale de experienta fara alterarea stariide constienta si cu libertate de miscare neingradita. In laboratorul de telemetrie se vor realiza studii din domeniul

cardiovascular si neurostiinte iar variabilele achizitionate vor fi reprezentate de presiunea arteriala, activitate electricacardiaca si activitate nervoasa vegetativa.

Zona Proceduri Chirugicale pentru Animale Mici si AnimaleMari

Tamba B, Iasi, 2016


Laborator PET/RMN animal mic

Evaluarea metabolismului celular ca marker al potentialuluimalign celular

Studiul biodistributiei unor medicamente noi prinradiomarcare,

Studiul biodistributiei unor nanoderivati si a mecanismului decaptare la nivelul unor tesuturi tinta

Studiul unor caracteristici fenotipice celulare in diferite boliprin intermediul unor radiotrasori cu mecanisme decaptare si cinetica celulara/tisulara in relatie cu o acestecaracteristici fenotipice

Studiul unor radiofarmaceutice deja utilizate dar incaincomplet studiate, pentru diagnosticul unor tipuri decancere, in scopul stabilirii de noi indicatii

Tamba B, Iasi, 2016


Laborator PET/RMN animal mic.

Studiul metabolismului glucidic al celulei tumorale curadiotrasori PET

Studiul in vivo, scintigrafic, al caracterului MDRtumoral, in relatie cu mecanismul de captare celularaa unor radiofarmaceutice

Studiul cineticii de captare celulara si biodistributiepentru un anumit radiofarmaceutic pe model animalsi corelarea parametrilor (influx/eflux) cu tipul celular(caracteristici fenotipice/potential malign)

Studiul unor radiofarmaceutice noi (conventionale siPET) pe model animal (etapa in studiulradiofarmaceuticelor noi)

Tamba B, Iasi, 2016


Laborator Ultrasound animal mic studii structurale si functionale in modele experimentale pe

animale mici, in vivo

investigarea progresiei diferitelor patologii si eficacitatiitratamentelor, precum si studii de dezvoltare embriologica.

studii translationale ale functiei cardiace si vasculare normale sipatologice,

dezvoltare de biomarkeri moleculari prin utilizarea de compusifunctionalizati, monitorizabili prin tehnologia de inalta rezolutie(~ 30 micrometri).

detectia precoce a tumorilor in modele experimentale, cuantificarea acestora in 2D si 3D precum si urmarirea in dinamica a vascularizatiei si proceselor de neoangiogeneza.

administrarea de terapii tintite la nivelul structurilor biologice de interes.

Tamba B, Iasi, 2016


Laborator Radiologie animal mare

studii structurale si functionale in modele experimentalepe animale mari, in vivo, permitand investigareaprogresiei diferitelor patologii si eficacitatii tratamentelor.

Tamba B, Iasi, 2016


Unitate Studii Functionale Celulare siMoleculare

Laborator Fiziofarmacologie studii "in vitro" pentru validarea tintelor terapeutice. studierea in vitro efectului anumitor produse medicamentoase

asupra disfunctiilor celulare precum si interactia dintre anumitemedicamente(droguri) si anumite tinte moleculare sau proteinede la nivel celular.

Laborator imagistica Celulara automatizarea tehnicii de imunomarcaj si hibridizare in situ (cu

marcaj flurescent FISH sau cromogen CISH) precum siextinderea activitatii catre tehnicile de microscopie avansata: microdisectie laser, morfometrie si caracterizare celularaindividula („Tissue Fax”) si de microscopie confocala.

Tamba B, Iasi, 2016


Unitate Studii Functionale Celulare siMoleculare

Laborator Analiza Moleculara Analiza de biodisponibilitate si bioechivalenta; Analiza PK si PD

noncompartimentala; Analiza toxicocinetica; Analizacompartimentala PK individuala; Rapoarte de analiza ale PK siPD.

Servicii de bio-analiza; LC-MS/MS, HPLC, LC-ICP-MS; Determinaribiochimice si imunologice; Determinari de fractii libere; Implementarea de noi tehnici de analiza; Dezvoltarea de noimetode si validari; Analiza probelor Non-GLP; Studii de metabolism si transport in vitro

Analize automate de biochimie pentru probele biologicerecoltate de la animal (ser, plasma, urina, etc) si de pregatire a probelor pentru LC/MS.

Tamba B, Iasi, 2016


Unitate Educationala si Multimedia

diseminarea rezultatelor cercetarii in cadrul activitatilorde invatamant licenta, cursuri postuniversitare, master, doctorat postdoctorat,

publicarea interna/internationala a datelor obtinute.

Tamba B, Iasi, 2016


CEMEX - oportunitati

dezvoltarea pe termen lung de colaborari cu alte structuri de cercetare clinica si fundamentala

rezultate stiintifice la nivel national si european, cu aplicatii directe in industria farmaceutica si biomedicala

Dezvoltarea de terapii inovative, elaborarea de studii de cercetare medicala in farmacologia fundamentala si farmacogenomica, validarea de noi protocoale de investigatii, screening si tratament prin studii de medicina experimentala

Obtinerea de brevete si patente din activitatea de cercetare care sa permita infiintarea de spin-off-uri si participarea la noi proiecte de finantare


Tamba B, Iasi, 2016


Tamba B, Iasi, 2016


Tamba B, Iasi, 2016


© http://www.phrma.org

Tamba B, Iasi, 2016


0

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2000 2002 2004 2006 2008 2010

$ B

illio

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R&D Spending Drug approvals (FDA)

Tamba B, Iasi, 2016


0

3

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AstraZeneca

GlaxoSmithKline

Novartis AGAmgen Inc. Apple

Romania

Sweden

R&D Spending / Drug

R&D Spending 2012 Total

R&D Spending 2011 Total

Tamba B, Iasi, 2016


Drug development

Basic Research

In Vitro Studies

Target Validation

Animal Models

Phase I and Phase II-PoC- Studies

Phase III Studies

Clinical ResearchForward Translation

Reverse Translation

(View drug developmentas customer)

(Feed back clinical needs and samples)

[van Gool et al, Drug Disc. Today 2010] Tamba B, Iasi, 2016


bioROne – biotechnology cluster

Location: North-East Romania

Year of creation: 2011

N° of members: 16

Sector of activity: biotechnology

Cluster strengths: 1 medical university, 2 research institutes, 3 clinical hospitals, and the largest

Romanian-owned pharmaceutical company. > 50 years of activity, > 100 research contracts and grants in last 5 years with a value

of over €50M (cumulative) Low-cost , high quality provider of research, development and manufacturing Incredible biotechnology pipeline with > 100 patents in the last 10 years.

www.biotechnologie.ro

Tamba B, Iasi, 2016


http://www.biotechnologie.ro

Cooperation today…

Tamba B, Iasi, 2016


Value chain analysis

Tamba B, Iasi, 2016


Membri: Universitatea de Medicina si Farmacie”Gr.T.Popa” Iasi,

www.umfiasi.ro

Universitatea Alexandru Ioan Cuza Iasi, www.uaic.ro

Spitalul Clinic Judetean de Urgente Sf. Spiridon Iasi www.spitalspiridon.ro

Spitalul Clinic de Recuperare, www.scr.ro

Institutul Regional de Oncologie Iasi

Directia de Sanatate Publica Iasi, www.dspiasi.ro

Directia de Sanatate Publica Neamt, www.sant.ro

Institutul de Medicina Legala Iasi – Institute of Forensic Medicine Iasi, www.imliasi.ro

Tamba B, Iasi, 2016


http://www.umfiasi.ro

http://www.uaic.ro

http://www.spitalspiridon.ro

http://www.scr.ro

http://www.dspiasi.ro

http://www.sant.ro

http://www.imliasi.ro

Membri: Institutul de Chimie Macromoleculara “Petru Poni” Iasi – Institute of

Macromolecular Chemistry "Petru Poni" Iasi – largest chemistry & polymers R&D institute in Romania, www.icmpp.ro

Institutul Naţional de Cercetare-Dezvoltare pentru Fizică Tehnică - IFT Iaşi -largest physics R&D institute in East Romania , www.phys-iasi.ro

SC Antibiotice SA – SME, generic drugs manufacturer for human use – largest Romanian owned producer, www.antibiotice.ro

SC A&B Pharm Corporation SRL – SME, Pharma retalier – largest independent pharmacy retailer in North-East Romania, www.abpharm.com

SC Romsoft SRL – SME, IT&C, www.rms.ro

Plantavorel – SME, aromatic & herbal plants products manufacturer, www.plantavorel.ro

Unic Pharmaceutical – SME, pharmaceutical wholesaler, import-export. , www.unicpharmaceutical.ro

Ircon – SME, generic drugs manufacturer for human use. , www.ircon.ro

Tamba B, Iasi, 2016


http://www.icmpp.ro

http://www.phys-iasi.ro

http://www.antibiotice.ro

http://www.abpharm.com

http://www.rms.ro

http://www.plantavorel.ro

http://www.unicpharmaceutical.ro

http://www.ircon.ro/

Aplicatii comerciale

obtinerea de patente

protejareaproprietatiiintelectuale

aplicatiicomerciale

ale cercetarilor

noi surse de finantare

Tamba B, Iasi, 2016


•Idee•Proof of concept•Patentare

•Fezabilitate•Valoare•First in human

•Validare•Aprobarea

utilizarii

•Utilizare clinica•Standarde de

tratament

Tamba B, Iasi, 2016


Tamba B, Iasi, 2016

Tamba B, Iasi, 2016

Untul pamantului(Tamus communis)

© tr

avel

-to-c

luj.b

logs

pot.c

om

Tamba B, Iasi, 2016

© O. C. Mungiu, 2012

[email protected]

www.biotechnologie.ro

Tamba B, Iasi, 2016

mailto:[email protected]

http://www.biotechnologie.ro

65Tamba B, Iasi, 2016

Va multumescDr. Bogdan IonelTamba

Centrul de Studiu si Terapie a Durerii

CEMEX, UMF Gr.T. Popa, Iasi, Romania

The future in drug development. Today. - adrnordest.roadrnordest.ro/user/file/news/16/prezentari_06_06_2016/WG 1... · 1973 - Laboratorul Central de Enzimologie şiFarmacologie Biochimică

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