md ethical and regulatory issues

7/31/2019 MD Ethical and Regulatory Issues

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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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12 Aug 2011 Medical device & Ethics 23

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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