TSU 2015 lecture 1 indro-market metals-ceramics ...lcr.tsu.ru/download/TSU_2015_lecture 1_indro-market_metals-cerami… · anesthesia equipment TSU_lecture 1_indroductionMT _WS_2008_K1+K2

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L. Heinrich Курзина И., Хейнрих Л.

Medical TechnologyМедицинская технология

- Basics, Materials, System Solutions -- основы, материалы, системные решения -

MT _WS_2008_K1+K2 1TSU_lecture 1_indroduction

Tomsk State UniversitySeptember/October 2015


Preliminary scheduleпредварительный план продолжиться

6 7 lectures each of 90 minutes in the morning & afternoon• 6 … 7 lectures each of 90 minutes, in the morning & afternoon6 … 7 лекций (90 минут), утром и после полудня

• exercises to the lecturesупражнения о лекциях

• written test on the content of the lectures on Monday afternoon (October 5th)письменный тест о содержании лекций в понедельник после полудня (5 октябрь)


• final and closing discussion and handing over the certifications on the successful participation in the course on Medical Technology on Tuesday morning (October 6th)финал и заключительное обсуждение и передача сертификатов успешного участия в курсе о Медицинской Технологии во вторник утром (6 октябрь)

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Literature & Links

Medical technology:

• Standard literatur such as

Basic medical literature(e.g. on physiology)is highly recommended• Standard literatur such as

- overviews on modern technologiesare not available on the internationalbook market!

Reasons:- huge varieties of materials, techniques andclinical applications

- huge dynamic of technological solutionsand innovative efforts (huge competion)

is highly recommendedas supplement


Useful links:www.rosminzdrav.ru/ (Министерсиво здравоохранения Руссийской Федерации),www.uspto.gov/patft/index.html (patent search at the US patent office)www.fda.gov (US Food and Drug Administration, e.g. status reports on medical devices, approvals etc.)www1.fips.ru/wps/wcm/connect/content_ru/ru/inform_resources/inform_retrieval_system/ (Russian patent office ----> search in the this data sources as “guest”)


Content

presently under preparation !p y p p


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Medical technology in retrospective view

anesthesia equipment


brain surgery

amputation of a leg

surgeoncase


New materials and technologies improve healt care

artifical heart valves

imaging techniques (e.g. MRT, CT) for diagnostics

heart pace maker

minimal invasive surgery


artificial heart incubators and monitoring systems using specific sensors

biomolecular analytics for diagnostics

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Further examples of modern medical technology

electron linear accelerator generating X rays

implanted chip (retina implant)

navigation and computer aidedsurgery


artifial heart cochlea implantat microarray for molecular biological

screenings & diagnostics


World market: ca. 200 bill. US$1. Medical device market

growth: ca 5 8% per year

USA34%

EU2513%

JapanAsia10%

others36%

Regions US$ mill.

USA ca. 80.000EU27 >30.000Japan 17.300China 2.400Russia (2013) 7 600

growth: ca. 5…8% per year


13%7%10%Russia (2013) 7.600

Source:The World Medical Market Fact Book 2009,EPISCOM BUSINESS INTELLIGENCE Publications,Chichester, UK

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Russia

Population (2014): 143 7 mill (74% are living in urban regions)Population (2014): 143,7 mill (74% are living in urban regions)growth rate (2013): +0,02 % (РОССТАТ), -0,04% (WORLD FACTBOOK)GDP (purchase power parity): 3.565 bill US$ (2014, WORLD FACTBOOK)

(USA: 17.420 bill US$, Germany: 3.722 bill US$, EU: 18.010 US$)

Exports: 530,3 bill US$Imports: 323,9 bill US$

Expenditures for health care: 6,5% of GDP


pExpenditures for education: 4,1% of GDP

Life expectancy : male: 63, female: 75 Sources:Федеральная служба государственной статистики (РОССТАТ): www.gks.ruCIA The World Factbook: www.cia.gov/library/publications/the-world-factbook/


2050: 120.896.000 (-17%)2010: 143.617.000

Population structure in the Russian Federation


Source: http://populationpyramid.net/russian-federation/

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предсказанный рост российского рынка

Health care system and medical device market in Russia

медицинского устройства


- free basic healthcare through the Mandatory Medical Insurance law,Russian healthcare system changes from a highly centralized to a decentralized one, divided on a federal, regional and municipal level. Apart from a guaranteed package of free services covered by the government, - Voluntary Medical Insurance (ДМС = Добровольное медицинское страхование )

covers additional services- out-of-pocket expenditures are rather high


Russian market situation:

imported medical devices valued at USD

leading international companies

Johnson & JohnsonG l El t i4,468.5 mn in 2014

(decline is expected)

examples of Russian medical deviceCompanies (> 2.500 manufacturers):

- ЗДРАВМЕДТЕХ (www.zmt.ru/)- ЭФА group (www.efa.ru/)- ЗАО "МЕДПРОМ" (http://medprom.spb.ru/)- JSC Elamed (www elamed com)

General ElectricBaxter InternationalAbbott3MBoston ScientificBraun MelsungFresenius medicalSiemens medical


- JSC Elamed (www.elamed.com)[Елатомский приборный завод]

- Яртек Медикал "Медицинские катетеры", (http://yamik.org/ru/ )

search on companies in Russia. http://medprom.ru/medpromwww.orgpage.ru/

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Fragmented market (large number of small i )

Characteristics of the medical device market

companies)

Only several internationally dominant companies (also present in Russia)

No player can totally contol the market

Consolidation (=mergers of small companies)

Causes :

Technology driven high innovation activities

Different market needs, manifold core compenties and product linies

L i l/ ti l diff i


(Vmarkt05 p

(=mergers of small companies)

Global growth: about 5% per year

Large regional/national differences in

- regulations (registration, permission)- financing the health care systems- national socio-economic performance

Cost pressure especially for basic medicalDevices (disposals, bandages etc)


Scientific and engineering disciplines involved in medical technology


• molecular biology(e.g. diagnostics)

• stem cell therapies • nanotechnologynano-medicine

• translational medicine

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Typical life cycles of technologies and products


Examples:ORStem: organ replacement on the base of pluripotent adult stem cellsCaidNS: computer aided navigation in surgeryRContr: remote contol of risk patients, telemetry, telematicLASIK: laser-assisted in situ keratomileusis; refractive eye surgery at corneaHeartPM: heart pace makers, also implanted defibrillators


2. Rough functional classification of medical devices(1/2)

• Implants (soft ... hard; active <---> passive)p ( p )

• Drug delivery systems

• disposals such ascatheters, sensors, drainages, tubings, connectors, valves, syringes etc.

• filter and membrane systems

i l d i d t l


• surgical devices and tools

• wound management systems, hygienic products

• orthopedic products, orthesis, fixatives

• diagnostic systems (e.g. microchips, biomelecular kits, PCR, DNA micro-arrays)

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complexe devices and data management (2/2)• functional (electro-)diagnostic devices⇒ cardiovascular, pulmonary and neurologic measurments

• imaging systems⇒ ultra sound, endoscopy, angiography, röntgen diagnosis,

tomography (MRT, CT …); alpha-, beta- & gamma scanning techniques

• therpeutic devices⇒ artificial respiration, heart-lung machine, heart pace maker, defibrillators,

radiotherapy, infusion pumps, dialysis, oxygenators, temperature management

• patient monitoring


• patient monitoring⇒ cardiovascular, respiration, cerebral and fetal

monotoring systems

• electronic data processing and management⇒ (on-line) data collecting & analysis, data networks, electronic expert systems,

telemetry, remote control (e.g. clinic and patient within home care,global patient monitoring & control systems


• in Russiaregistration at Ministry of Health of Russia and certification as medical device

3. Legal requirements to market medical devices

(GOST R certification) ---> http://medexpert.ru/document/registration/61/ [valid over a period of three years]

• in the EU:only products labeled with the CE tag are permited to access the market= CE certification ! (§ 6 (1) und § 7 MPG = EU guideline 93/42/EWG)

document of conformity permits the use of the CE label fixed on the product= “passport for supply” within the EU countries


• in US:certification according the FDA rules is necessary (www.fda.gov)

Supplying any medical devices in foreign countries:The national legal requirements must be fulfilled: registration + certification

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3.1. Classification of medical devices according the potential risks(GOST R 51609-2000 Medical devices) = similar to EU(GOST R 51609 2000 Medical devices) similar to EU

class 1 class 2a class 2b class 3

• low risks• minal contact to skin• non-invasive• short application

Examples:

• average risks• low level ofinvasion

• timely limitedapplication (≤ 30days)

• increased risks• long time application≥ 30 Tage

• systemic effectsExamples:

anesthesia

• high degree of risks • apllications at heart,central cardiovascularsystem or centralnervous system

Examples:


Examples:- surgery clothes,- bandages without

direct skin contact- some surgical

equipments

y )Examples:- Ultrasound devices

for diagnostics- short time catheters

(not near the heart)

- anesthesia machines

- PCR catheters- condoms- administration of

drugs

p- heart pace makers- invasive

contraconceptiva- stents- artificial heart

valves


3.3. Safety concept for medical devices


GMP = Good Manufacturing Practice (DIN EN ISO 9000 ff, Guidelines EU)GLP = Good Laboratory PracticeGCP = Good Clinical Practice (Richtlinie: 2001/20/EC)

standardization, regulations and laws are under steady changes!

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4. Biomaterials, biocompatibility

rawmaterials

Upgradingto achieve


Biocompatibilityis the ability of a material

to perform with an appropriate hostresponse in a specific application

(European Society for Biomaterials, 1986)


Requirements of Biocompatibility

structural biocompatibilityp y• fitted design• mechanical performance• anisotropy/isotropy• structural mimicry• morphology/texture

• weight & force transfer• tribology

biofunctionalitysignal transmission in subretinal implants(Hopkins Univ.; Bio World 4/1999, p. 14)

surface biocompatibility


• tribology• resistance to wear• optical & acoustic transmission• bioresistance/controlled

biodegradation

• controlled interactionwith the biological system

• hemocompatibility• minor immune response• no cell activation• no release of remaining mono-

mers or additives

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5. Materials in Medical Technology

5.1. metals (+ alloys)5.2 ceramics, glass

5.3. polymers(synthetic, natural;


bioresistent, biodegradable)


5.1. Metallic devices (examples)

Knee, hip and shoulder prosthesis, fixation elements tostabilize fractures, stents (e.g. vascular), screws and wires( g )

Stents


artificial hip jointbone plates andscrews

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stainless/alloyed steel,CoCr(Mo) alloys AuAg alloys

Implantable metals

- mechanical strength- resistant against corrosion- biokompatibility- non-allergene

CoCr(Mo) alloys, AuAg alloys,cp (commercially pure) titanium and titanium alloys (e.g. TiAl6V4)

requirements:


risks:- corrosion (after distroy of passive layers),pitting corrosion and stress cracking

- wear- material fatigue- loosening of prosthesis (aseptic/septic loosening)


metallic materials applications (examples)

316, 316L,ll d t l

bone fixation (bone fractures)joint replacementalloyed steel joint replacementspinal implantsstentssurgical instruments/tools

titanium, mostly used as alloyssuch as TiAl4V6, TiNb13Zr13

bone and joint replacementdental implants

CoCr(MO) alloys bone and joint replacement


dental implantsartifial heart valvesstents

Au alloys,Au, Pt

heart valves, middle ear implants,dental technology (e.g. crowns, inlays),sensors

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Corrosion & adverse effects

Me Me n+ + n e -

O + 4 e - + 2 H O 4 OH - broken f h ftO2 + 4 e + 2 H2O 4 OH

4 H + + 4 OH - 4 H2O

caused by local electrochemical elements• between different metals• intercrystalline electrochemisty

femour shaft(hip jont implant)

• corrosion caused crack growth --> break,ibl t i ff t t i ti


broken metallic fixture of a heart valve

possibly toxic effects, mutagenic reaction,or allergic effects (e.g. Ni sensivity)

• wear ---> reduced tribology, particlescause inflammation and/or osteolysis,implant loosening

• fatigue ---> break


Titaniumcp Titan: unalloyed commercially pure titanium = α-titanium,

hexagonal close-packing of spheres, crystal positionsffcan be exchanged with different metals; low strength

TiAI6V4 : cubic centered crystal structur = β−titanium alloy,applied as crystalline mixed phase: „α−β−titanium“enlarged strength, improved stability against fatigue

thermaltreatment


dental implant;rough texture improvesthe osseointegration(coatings with Ca apatiteare also used)

titanium implantsof individually adjusted geometry(cranial plates)

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5.2. Biocompatible ceramic materials

Bioceramics:mainly Al and Zr oxides glass ceramics as artificial teeth (adjusted colors)mainly Al and Zr oxides, glass ceramics as artificial teeth (adjusted colors),Ca phosphate (Ca5(PO4)3OH = HAP) as coatingson implants or in bone repair products


joint components for hip and prosthesis dental implantsmade from ZrO2


Corrosion effects on ceramic materials• “baked” ceramics (treated at < 800 °C) and glass

= surface corrosion by partial dissolutiond b id d OHcaused by acids and OH-

surface destruction, increasing roughnessand pore formation ---> increasing wear

• high temperature treated ceramics ---->biologically intert of different porosities,improved fracture and crack resistance

• hydrothermally produced and high pressure-thermally

jont replacement by ceramics


hydrothermally produced and high pressure thermally manufactured glass ceramics---> no pores, stronly closed ultrastrukture

chemically resistantstrong scratch resistanthigh pressure, crack and fracture resistance

glass ceramics manufacturedfor dental crowns

Risks: wear (inflammation), over-loading induced breaks (focal failures)

Documents

TSU 2015 lecture 1 indro-market metals-ceramics ...lcr.tsu.ru/download/TSU_2015_lecture 1_indro-market_metals-cerami… · anesthesia equipment TSU_lecture 1_indroductionMT _WS_2008_K1+K2