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Medical Device Evaluation
Muraleedharan CV
Ethical & regulatory issues
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What are medical devices ?
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What are medical devices ?
any instrument, apparatus, appliance, material or other
article, including the software
intended to be used for human beings for the purpose of:
diagnosis, prevention, monitoring, treatment or alleviationof disease, or compensation for an injury or handicap
control of conception
does not achieve its principal intended action by
pharmacological, immunological or metabolic means
But, could be aided by such means
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Medical devices range
About 1.5 million different devices
Consist of 900 product groups, covering 50clinical specializations
Broadly classified as
Diagnostic devices ( Medicalinstrumentation, testing kits and
reagents)
Therapeutic devices (Implantables,
Disposables & Reusables )
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Medical devices global market
World Market in 2008 ~ $300 BillionSource WHO MEDICAL DEVICE REGULATIONS
Global overview and guiding principles - 2005
0
10
20
30
40
50
60
70
80
U S
$ ( B
i l
l i o n
)
2004 Market
US
Europe
JapanLatin America
China
India
Others
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Medical devices Indian market
Healthcare sector 5.5 % of GDPRs.170,000 crores
Pharmaceutical sectorRs.30,000 crores
Medical devices ~ Rs.12,000 crores
Medical InstrumentationRs.15,000 crores
Annual growth rate : 10 - 12%
75 80 % met by imports
Indigenous production : ~ Rs.2,400 crores
Source : CII McKinsey Report on Healthcare in India 2010 &
Indian Market Estimates HIMA, USA , 2008
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Medical devicesIndias strengths
Strong and well developed healthcare segment
11500 hospitals and 14000 diagnostic laboratories
Performance in pharmaceuticals segment
Human resource availability
> 500 research institutions, 400 universities
Second largest pool of scientists and engineers
Youngest work force amongst growing economies
Fast growing internal market
Shift in disease pattern from infectious to life style related
Expanding rich and middle income group
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Indias competitive advantage
HR Strength, Productivity, Quality
English language advantage
India
PhilippinesMexico Israel
Ireland
Indonesia
Turkey
Brazil
Russia
China
LOW HIGH
Projected work
force in 2020
Short fall
Surplus
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Medical devicesIndias weaknesses
Very little industrial R&D
Lack of adequate preclinical evaluation facilities
Shortage of training facilities for medical device segment
Research and development
Good manufacturing practice
Regulatory issues and product certification
Limited availability of information
Weak national regulatory system
focus on ethical reviews for human protection
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Medical device - life cycle
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Assurance of medical device safety
Absolute safety cannot be guaranteed
A risk management problem
Closely aligned with device effectiveness / performance
Requires shared responsibility among the stakeholders
Risk based approach
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Risk based classification
CLASS RISK LEVEL DEVICE EXAMPLES
I Low Risk Surgical instruments / tonguedepressors
IIa Low-moderate Risk Hypodermic Needles / suctionequipment
IIb Moderate-high Risk Lung ventilator / orthopaedic
implants, blood bags
III High Risk Heart valves / implantabledefibrillator / shunts
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Level of regulation to risk
Device ClassI IIa IIb III
Increasing risk
Regulatory
requirements
Low
High
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Medical device Vs drugs
Short product cycles ~ 5 - 20 years
Large variety of mechanisms of action
Can fail due to myriad of faults
mechanical, electrical, electronics, software (logical), etc Great variety of scientific disciplines involved
Engineering, materials science, nuclear and radiation,
biological sciences
Can fail after many years in a manner not predictable initially
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Medical device Vs drugs
Failure Modes Minimal :
Toxicity, pharmacological function,
side effects, removal from body
Gets qualified through
Preclinical safety evaluation
Phase 1 Clinical safety evaluation
Phase 2 efficacy
Phase 3 wider efficacy studies
Phase 4 : PMS
Failure Modes Biocompatibility
Electronic instrumentation / Software
Hemodynamics (blood contacting devices)
Radiation Biological materials / Biodegradation
Nano materials
.
are more multi disciplinary, complex thanDRUGS
An approach different from that of drugs is required for
regulating medical devices
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Pillars of human protection
REGUL
ATORY
MECHA
NISM
ETHICALREVIEW
Rights & welfare of human subjects
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Lack of regulatory framework
Patients / Clinicians Compromise on safety & quality
assurance
Industry no product certification for market acceptance
only way -- get CE Mark or FDA approval - expensive & time
consuming
Non-tariff barriers to trade in developed economies
R&D labs developing medical devices Difficulty in introducing into clinical trials / use
No agency to assure safety
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Lack of ethical review
Patients / Clinicians No independent review lack of
confidence in the device
Industry Data generated does not get accepted by
regulatory bodies
Waste of effort and resources
R&D labs developing medical devices
Difficulty in introducing into clinical trials / use
No legal protection
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Ethical guidelines
Ethical guidelines for biomedical research onhuman subjects, ICMR, 2000 (Revised 2006)
Guidance document on the humane care of
animals in experimental research, ICMR, 2006
National guideline for stem cell research andtherapy, 2006
Ethical guidelines for biobanking in India, ICMR,
2004
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Status of regulation in India
1982 Amendments to Drug and Cosmetics Act, 1940
Drug to include Devices intended for internal or external
use in the diagnosis, treatment, mitigation or prevention of
disease 2006 : DCGI notified a set of products uses drug
approach
Only a small segments of the entire medical device
spectrum is covered Documentation on regulatory mechanism and compliance
requirements are not adequate
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Ensuring device safety
Before useMED DEVICE REGULATION
Manufacturer
Regulatory authority
Conformity Assessment Body(Notified body)
During useHOSPITAL ACCREDITATION
Clinician
Hospital
Clinical engineers Accreditation requirements
NABH
After use1. Post-market surveillance by manufacturer
2. Vigilance by regulatory authority
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Device safety Technical assessment
Pre-clinical evaluation Design control, validation and risk / reliability analysis
-
Materials qualification
Physical and chemical characterisationBiocompatibility evaluation
in vitro device evaluation in simulated systems
In-vivo evaluation in large animals
Quality systems & Good Manufacturing Practices
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8-Aug-12 Medical device & Ethics 24
CLINICAL INVESTIGATION OF MEDICAL DEVICES
ISO 14155 : 2011
Clinical investigation of medical devicesfor human subjects -- Good clinical
practice
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Case study Chitra Heart Valve (ISO 5840) Monocentric safety study 40 valves / 1 year
Multicentric safety & performance
+ 266 added in 5 additional centres
Results compared with historical data of established mechanical valves.
PLACEBO / BLINDING / RANDOMISATION ?
Prospective control needed ?
Would it improve the validity of the study?
Single blinding / Randomization would it improve the validity of the study?
Controls
Starr-Edwards ball valve Rs. 25,000 ea. - not comparable ?
Medtronic-Hall tilting disc Rs. 35,000/- ea. comparable ?
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Case study -- Membrane oxygenator (ISO 7199) Monocentric safety study 25 devices
Multicentric safety & performance - additional 150 patients in 6 centres
No blinding / No randomisation
Patients consenting for test device Test group
Others asked for consent to be part of Control group
Is this acceptable ?? Test group device free (without prior info) other expenses charged except for
additonal tests over standard of care.
Control group charged except for any additional tests
? Single blinding / Randomisation would it make the study better ?
? Cost of imported control device ??
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Other issues
Adverse event reporting
Device related vs. non-device related
Statistical analysis and methodology
Especially long term follow-up studies for implantable
devices
Insurance coverage
Now available for clinical evaluations from Indiancompanies
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