The document outlines the clinical investigation and evaluation processes for medical devices and in vitro diagnostics (IVDs), detailing definitions, regulatory frameworks, and classification systems across different jurisdictions. It emphasizes the importance of systematic investigations to assess safety and effectiveness, following established guidelines and ethical considerations. Furthermore, it stresses the need for comprehensive clinical evaluation procedures, incorporating both pre-market and post-market data to ensure compliance with safety and performance standards.

1. CLINICAL INVESTIGATION AND
EVALUATION OF MEDICAL DEVICES AND
IVDS
Prepared by,
Faizan Shaikh
M.Pharm (Sem – 1 )
Pharmaceutical Regulatory Affairs

2. CONTENTS
1. Introduction
2. Clinical investigation
3. Objective
4. General principles
5. Conduct of clinical investigation
6. Ethical consideration
7. Clinical evaluation
8. General principle
9. Clinical research report
10.References
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3. DEFINATIONS
As per USFDA-
 An instrument, apparatus, implement, machine, contrivance,
implant, invitro reagent or other similar or other article, including
a component part, or accessory which is recognized in the official
National formulary or USP or any supplement to them ,intended
for use in diagnosis of disease or other condition or in the
intended, or prevention of other diseases in men and animals or
intended to affect structure or any function of the body of man or
other animal, and
 Which does not achieve any of it’s primary intended purpose
through chemical action within or on the body of man or other
animal which is not dependent being metabolized for the
achievement of any of its primary intended purposes
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4. As per D & C Act,
Instrument intended for internal or external use in
the prevention of disease or disorder in human
being or animal as may be specified from time to
time by central government by notification in the
official gazette, after consultation with the board
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5. Definition
 In India, at present only notified medical devices are regulated as
Drugs under the Drugs and Cosmetics Act 1940 and Rules made there
under in 1945
1. (1) substances used for in vitro diagnosis and surgical dressings,
surgical bandages, surgical staples, surgical sutures, ligatures, blood
and blood component collection bag with or without anticoagulant
covered under sub-clause (I);
2. (ii) substances including mechanical contraceptives (condoms,
intrauterine devices, tubal rings), disinfectants and insecticides
notified under sub-clause (ii); and
3. devices notified from time to time under sub-clause (iv), of clause (b)
of section 3 of the Drugs and Cosmetics Act, 1940;
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6. Definitions
IVDS,
 Definition: In vitro diagnostic products are those reagents,
instruments, and systems intended for use in diagnosis of disease or
other conditions, including a determination of the state of health, in
order to cure, mitigate, treat, or prevent disease or its sequelae. Such
products are intended for use in the collection, preparation, and
examination of specimens taken from the human body. [21 CFR 809.3]
 IVDs are devices as defined in section 201(h) of the Federal Food,
Drug, and Cosmetic Act, and may also be biological products subject to
section 351 of the Public Health Service Act. Like other medical
devices, IVDs are subject to premarket and post market controls. IVDs
are generally also subject to categorization under the Clinical
Laboratory Improvement Amendments (CLIA '88) of 1988.
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7. CDSCO (IMRDA) & MDD risk based
classification
Class A (Class-1)-Devices involving low risk levels
(Thermometer)
Class B (Class-2a)-Devices involving low to medium
risk (Hypodermic needle)
Class C (Class 2b)-Devices involving moderate to high
risk (Lung ventilator)
Class D (Class 3)-Devices involving high risk (Heart
valve, Implantable devices)
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8. Classification
By USFDA,
• Class-1 (low risk)-Elastic bandages, examination
gloves, adult incontinence pad
• Class-2 (Medium risk)-Catheter gloves, adult syringe,
needle
• Class -3 (High Risk)-Pacemakers, dental lasers, heart
valves
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9. Clinical Investigation
 A clinical investigation is defined as any systematic
investigation or study in or on one or more human subjects,
undertaken to assess the safety, clinical performance and/or
effectiveness of a medical device.
 The undertaking of a clinical investigation is a scientific process
that represents one method of generating clinical data.
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10. Clinical Investigation
Objective
The objective of a clinical investigation is to
assess the safety, clinical performance and/or
effectiveness of a medical device for a particular
indication or intended use.
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11. How it conducted?
ISO 14155: 2011 Clinical Investigation of
Medical Devices for Human Subjects — Good
clinical practice details the requirements for
the conduct of clinical investigations. Clinical
investigations must take into account scientific
principles underlying the collection of clinical
data along with accepted ethical standards
surrounding the use of human subjects.
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12. Essential Principle applicable to all Medical
Device and IVDS
When should Clinical Investigation conducted?
Clinical investigations are necessary to provide data not
available through other sources (such as literature or
nonclinical testing)
When considering the need for a clinical investigation, one
should consider whether there are new questions of safety,
clinical performance and/or effectiveness for the particular
medical device and intended use that need to be addressed
in a clinical investigation.
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13. Key consideration in clarifying need of Investigation
1.Identifying relevant clinical Essential Principles (for
example, specifics of safety, clinical performance,
acceptability of benefit/risk) for the medical device and its
intended use/purpose(s)
2.Performing risk management activities such as a risk
analysis will help in identifying the clinical data necessary
3.Conducting proper clinical evaluation demonstrates which
clinical data necessary
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14. 14

15. General principle for conducting investigation
Any clinical
investigation
must,
Be based on the results of the clinical
evaluation process
Follow a proper risk management procedure
to avoid undue risks
Be compliant with all relevant legal and
regulatory requirements
Be appropriately planned, conducted,
analyzed and reported
Follow appropriate ethical principles
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16. Other factors include,
 Type of Medical Device and/or regulatory classification
 Novel technology/relevant previous experience
 Clinical application/indications
 Nature of exposure to the product (e.g. surface
contact, implantation, ingestion)
 Risks inherent in the use of the product (e.g. risk
associated with the procedure)
 Performance claims made in the medical device
labeling (including instructions for use) and/or
promotional materials
 Component materials or substances
16

17. CONTI…..
 Demographic, geographic and cultural considerations (e.g. age,
ethnicity, gender)
 Potential impact of device failure
 Period of exposure to the medical device
 Expected lifetime of the medical device
 Availability of alternative treatments and current standard of
care
 Ethical considerations
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18. Clear statement of objectives
Minimization of risk to subjects and those involved with
the conduct of the investigation
Adverse event definitions and reporting
Study endpoints
Appropriate subject population(s)
Minimization of bias (e.g.randomization,
blinding/masking, concealment of allocation)
Identification of confounding factors (e.g. concurrent
therapies, co-morbidities)
Factors needing consideration in
study protocols include:
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19. CONTI…..
 Choice of Appropriate controls (e.g. active control, sham,
historical
 Design configuration (e.g. parallel, crossover, cohort
study, single arm)
 Type of comparison (e.g. superiority, non-inferiority,
equivalence)
 Follow-up duration and monitoring
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20. In designing the study, Development of a statistical plan should include
consideration of the following:
 Clinically relevant endpoints
 Analysis population
 Statistical significance levels, power
 Sample size calculation and justification
 Analysis methodology
 Management of potential confounding factors
 Procedures for multiplicity control and adjustment of error probabilities
 Procedures for handling of missing, unused or spurious data, including
drop-outs
 Procedures for handling deviations from the original statistical analysis
plan
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21. Conduct of Clinical Investigation
A properly conducted clinical investigation, including
compliance to the clinical investigation plan and local laws
and regulations, ensures the protection of human subjects,
the integrity of the data and that the data obtained is
acceptable for the purpose of demonstrating conformity to
the Essential Principles. ISO 14155 outlines good clinical
practice for clinical investigations of medical devices
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22. Final study Report
The outcome of a clinical investigation should
be documented in a final study report. This
then forms part of the clinical data that is
included in the clinical evaluation process and
ultimately becomes integrated into the
clinical evaluation report
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23. Ethical
consideration for
conducting
investigation
It should generate new data and answer specific safety,
clinical performance, and effectiveness questions that remain
unanswered by the current body of knowledge.
The desire to protect human subjects from unnecessary or
inappropriate experimentation must be balanced with the
need to protect public health through the use of clinical
investigations where they are indicated.
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24. Clinical Evaluation of Medical Devices and IVDs
Clinical Evaluation
Clinical evaluation is a set of ongoing activities that
use scientifically sound methods for the assessment
and analysis of clinical data to verify the safety,
clinical performance and/or effectiveness of the
medical device when used as intended by the
manufacturer.
.
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25. When is Clinical Evaluation undertaken?
 It is first performed during the development of a
medical device in order to identify data that need to
be generated for regulatory purposes and will inform
if a new device clinical investigation is necessary,
together with the outcomes which need to be studied.
This information is fed into the ongoing risk
management process (according to ISO 14971:2007)
and may result in changes to the manufacturer's risk
assessment, clinical investigation documents,
Instructions for Use and post market activities.
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26. Why Clinical Evaluation important?
• When placing a medical device on the market, the
manufacturer must have demonstrated through
the use of appropriate conformity assessment
procedures that the medical device complies with
the Essential Principles of Safety and Performance
of Medical Devices.
• Generally, it is expected that the manufacturer
has demonstrated the medical device achieves its
intended performance during use according to its
labelling (i.e. information supplied by the
manufacturer) and that the known and
foreseeable risks are minimised and acceptable
when weighed against the benefits.
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27. What is the process?
To conduct a clinical evaluation, a manufacturer needs to:
 Identify the Essential Principles that require support from
relevant clinical data;
 Identify available clinical data relevant to the medical device
and its intended use;
 Evaluate (appraise and analyses) clinical data in terms of its
suitability and contribution to demonstrating the safety, clinical
performance and/or effectiveness of the medical device in
relation to its intended use
 Generate clinical data needed to address remaining
questions of safety, clinical performance and/or effectiveness;
 Bring all the clinical data together to reach conclusions about
the safety, clinical performance and/or effectiveness of the
medical device
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28. General principle for Clinical Evaluation
 The clinical evaluation is based on a comprehensive
analysis of available pre- and post-market clinical data
relevant to the intended use of the device in question,
including safety, clinical performance and/or
effectiveness data.
 There are any design features of the medical device or
target treatment populations that require specific
attention.
 Whether data from comparable devices can be used to
support the safety, clinical performance and/or
effectiveness of the device in question.
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29. STAGES OF CLINICAL EVALUATION
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30. STAGE 1 DATA IDENTIFICATION
A. Data generated through literature searching
B. Data generated through clinical experience
C. Data from the clinical investigations
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31. Data or document required for the clinical evaluation,
The clinical investigation plan;
 Clinical investigation plan amendments and the rationale for
these changes;
 The relevant Ethics Committee documentation, opinion(s) and
comments for each investigation site, including a copy of the
approved informed consent form(s) and patient
information documents;
 Case report forms, monitoring and audit records;
 Regulatory Authority approvals and associated correspondence
as required by applicable regulations;
 The signed and dated final report
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32. STAGE 2 APPRAISAL OF CLINICAL DATA
PURPOSE
 Each piece of data is appraised to determine its suitability to address
questions about the device, and its contribution to demonstrating the
safety and performance of the device (including any specific claims about
safety or performance).
APPRAISAL COVER SHOULD INCLUDE,
 In addition, any reports or collection of data should contain sufficient
information for the evaluator to be able to undertake a rational and
objective assessment of the information and make a conclusion about its
significance with respect to the performance and safety of the device in
question. It should be assessed for its quality and for its relevance to the
device in question (i.e. the data must be either generated for the device
in question or for a comparable device) and its intended use.
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33. STAGE 3 ANALYSIS OF CLINICAL DATA
 The goal of the analysis stage is to determine if the
appraised data sets available for a medical device collectively
demonstrate the clinical performance and safety of the
device in relation to its intended use
The methods available for analysis of clinical data generally
are either quantitative or qualitative.
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34. As a final step the evaluator should consider the basis
on which it can be demonstrated that the combined
data show:
The device performs as intended by the
manufacturer
The device does not pose any undue safety
concerns to either the recipient or end-user; and
Any risks associated with the use of the device are
acceptable when weighed against the benefits to
the patient.
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35. CLINICAL RESEARCH REPORT
 At the completion of the clinical evaluation process a report should be
compiled that outlines the scope and context of the evaluation; the inputs
(clinical data).
 The appraisal and analysis stages; and conclusions about the safety and
performance of the device in question.
 The clinical evaluation report should contain sufficient information to be
read as a stand alone document by an independent party (e.g. regulatory
authority or notified body).
 The technology on which the medical device is based, the intended use of
the device and any claims made about the device’s clinical performance or
safety
 The nature and extent of the clinical data that has been evaluated; and
 How the referenced information (recognized standards and/or clinical data)
demonstrate the clinical performance and safety of the device in question.
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36. REFRENCES
1. GHTF SG1/ N044:2008 Role of Standards in the Assessment of Medical Devices,
02/01/2023
2. GHTF SG1/ N071:2012 Definition of the Terms ‘Medical Device’ and ‘In Vitro Diagnostic
(IVD) Medical Device’ 02/01/2023
3. GHTF SG1/ N78:2012 Principles of Conformity Assessment for Medical Devices
02/01/2023
4. IMDRF GRRP WG/N47 FINAL: 2018 Essential Principles of Safety and Performance of
Medical Devices and IVD Medical Devices 01/01/2023
5. GHTF/SG1/N45:2008 Principles of In Vitro Diagnostic Medical Devices Classification.
01/01/2023
6. https://www.fda.gov/training-and-continuing-education/cdrh-learn/overview-regulatory-
requirements-medical-devices 29/12/2022
7. https://cdsco.gov.in/opencms/opencms/en/Medical-Device-Diagnostics/ 29/12/2022
8. https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-
documents/IVD/FAQs/FAQ_IVD_MDR-2017_2.pdf 29/12/2022
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37. THANK YOU
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