this topic deals with the regulation of medical devices in relation to FDA IN USA and CDSCO of INDIA.

1. MEDICAL DEVICE TRIALS
- DR. MOHAMMED UMAR SHARIEF

2. OBJECTIVES
 Define medical device
 Describe the classifications of devices
 Describe the ways a device can get to market
 Describe how medical device clinical trials differ
from drug trials

3. MEDICAL DEVICE DEFINITION
 • An instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent, or other similar article, including any
component, part, or accessory which is:
 – Recognized in the official National Formulary, or the
United States pharmacopeia, or any supplement to them
 – Intended for use in the diagnosis of disease or
conditions, or in the cure, mitigation, treatment, or prevention
of disease in man or other animals
 – Intended to affect the structure or any function of the
body of man or other animals
 • Which does NOT achieve its primary intended purposes
through chemical action within or on the body of man or other
animals and which is NOT dependent upon being metabolized
for the achievement of its intended purposes.

4. THE IMPORTANT POINTS
 Device definition excludes products that:
 Achieve their primary intended purpose through
chemical action within the body
 Are dependent upon being metabolized for the
primary achievement of their primary intended
purposes

5. MEDICAL DEVICES ARE CLASSIFIED BY RISK
Class I Devices
General controls are sufficient to provide
reasonable assurance of the safety and
effectiveness
Typically present the lowest potential for harm
and are simpler in designs.
Examples: elastic bandages, examination gloves,
and hand-held surgical instruments.

6. GENERAL CONTROLS
 Prohibition against adulterated or misbranded
devices
 Premarket notification 510(k) requirements
 Good Manufacturing Practices (GMPs)
 Labeling
 Registration of manufacturing facilities
 Listing of device types
 Record keeping
 Repair, replacement or refund

7.  Class II Devices
-General controls alone are insufficient to assure
safety and effectiveness, and existing methods are
available to provide such assurances.
-Carry moderate risk to patients.
-Also subject to special controls
Examples: powered wheelchairs, infusion pumps,
and surgical drapes

8. SPECIAL CONTROLS
 Performance standards (discretionary, voluntary
national or international standard, recognized by
rulemaking)
 Post-market surveillance
 Patient registries
 Development and dissemination of
guidelines/guidance's
 Design controls
 Recommendations and other appropriate actions
 Tracking requirements

9.  Class III Devices
-Insufficient information exists to determine that
general and special controls are sufficient to
provide reasonable assurance of the safety and
effectiveness of such devices
-Such devices are:
1. Life sustaining or life supporting
2. Substantial importance in preventing impairment of
human health; or
3. Present unreasonable risk of illness or injury

10. FDA REQUIREMENTS
 FDA Overview
 Device Classifications / Submission Types
 Approval / Clearance Requirements
 Investigational Devices
 Combination Products
 US Agent / Establishment Registration

11. GETTING A DEVICE TO MARKET
 Premarket Notification 510(k)
-Used for devices that are substantially
equivalent (SE) to a predicate device
-Manufacturer must notify FDA 90 days before
proposing to market a device
-Burden is on the manufacturer to demonstrate
that the device is SE.
. The device is as safe and effective as an existing
marketed device..

12. 510(K) REQUIREMENTS
 Description of the new device
– Photographs
– Engineering drawing
 Labeling – Draft promotional materials
 Identification of predicate device(s)
 Narrative and tabular comparisons
 Predicate device’s intended use, indications
 Technological characteristics
 Principles of operation
 Software documentation
 Sterility information
 Biocompatibility information

13.  Statement or declarations of conformance to
applicable standards and guidance documents
 Summaries of any performance testing
 Administrative requirements
– Truthfulness and accuracy statement
– 510(k) summary
– Payment of a user fee

14. SUBSTANTIAL EQUIVALENCE
 • A device is substantially equivalent to a legally
marketed predicate device
– Both have the same intended use
– Same technological characteristics or;
– Different technological characteristics do not
raise any new questions of safety or effectiveness
and performance data that demonstrates the new
device is as safe and effective as the predicate
device
• Bench
• Animal
• Clinical data

15. SUBSTANTIAL EQUIVALENCE ANALYSIS
 Intended use / indication for use
 Technological characteristic
 Clinical trials
 Conclusions
 If the FDA concludes substantially equivalent
– Issue an order granting 510(k) clearance
 If the FDA concludes not substantially equivalent
– The device is a Class III, requires PMA approval
– Unless the FDA reclassifies into Class I or II

16. DE NOVO DOWN CLASSIFICATION
• FDA issues a not substantially equivalent
• Two options
– Proceed with submission of a PMA
– Petition the agency in writing for De Novo down
classification within 30 days of receipt of the letter
• To qualify, the device must be both “novel and low
risk”
• Novel – Limits to not previously classified FDC Act
and classified by written notice
• Low Risk – Application to lower-risk devices the
agency has found not substantially equivalent for
the lack of a predicate device.

17. • Within 30 days
• Description of the device
• Labeling
• Justification for recommendation classification
• Information to support the recommendation
including
– Bench – Animal – Human clinical data
• Usually clinical data is required

18. PREMARKET APPROVAL APPLICATION (PMA)
 Class III devices
 New types of devices
 Previously found not SE
 May require pre-clinical and clinical data obtained
from an investigational device exemption (IDE)

19. PMA REQUIREMENTS
 Must demonstrate the safety and effectiveness of a
new device supported by valid scientific evidence
 Convenes an advisory committee
 Nonbinding recommendation to FDA
 FDA inspects the manufacturer’s facilities to QSR
 FDA issues an Approval letter or;
 Non approvable, which identifies the major
deficiencies

20.  Complete description of the device
 Complete description of the components
 – Photographs
 – Engineering drawings of the device
 Detailed description of the methods, facilities and
controls used to manufacture
 Prepared labeling, advertising literature, any
training material

21.  Software documentation
 Sterility information
 Biocompatibility information
 Extensive clinical trials
 Animal studies
 Bench tests
 Published and unpublished literature
 Bibliography of all published reports known
concerning the device’s safety or effectiveness

22. INVESTIGATIONAL DEVICE EXEMPTIONS
 Devices that are not approved or cleared and are
used in clinical trials must be labeled as
Investigational Devices “IDE”
 • The FDA may request
– Submission of animal or human clinical
data to demonstrate equivalence or safety and
effectiveness of a device
– Significant risk
– Prior approval by an Institutional Review
Board (IRB)
– Informed consent of patients
– FDA approval of an IDE application

23. IDE APPLICATION
 21 CFR Part 812
 Clinical study protocol
 A significant risk device study
– Potential for serious risk to health, safety or welfare
to the subjects
– Intended as an implant
– Used in supporting or sustaining human life
– Substantial importance in
• Diagnosing
• Curing
• Mitigating or treating a disease
• Prevents impairment of human health
– Potential for serious risk to health, safety or welfare
of a subject

24.  • Non significant risk (NSR) investigated device
– Requires IRB approval
– Informed consent
– Need not obtain FDA approval before study
begins

25. DEVICE TRIALS ARE UNIQUE
 Trials tend to be smaller than drug trials
 Some novel, many “me-too”
 Many difficult to blind, randomize, control
 Many depend on physician technique
 Device modifications occur during trial
 Endpoints highly diverse
 Typically, single pivotal trial follows feasibility
stage(s)
 Designed to support a “reasonable assurance of
safety and effectiveness” for the marketing
application

26. TYPES OF IDES
 Feasibility study
– May provide support for a future pivotal study or
may be used to answer basic research questions
– Not intended to be the primary support for a
marketing application
– Endpoints and sample size generally not
statistically driven
– Often required by FDA prior to pivotal study to
assess basic safety and potential for effectiveness
– Generally ~10-40 patients but may be larger
– FDA review is primarily focused on safety and
whether the potential benefit or value of the data justifies
risk

27. TYPES OF IDES
 Pivotal study
– Generally intended as the primary clinical
support for a marketing application
– Designed to demonstrate a “reasonable
assurance of safety and effectiveness”
– Endpoints and sample size statistically driven
– Designed to assess both safety and
effectiveness
– FDA review is much more complex

28. FDA’S FEASIBILITY IDE REVIEW
 Focused on safety
 Critical issues
– Reasonable study conceptually?
– Adequate preclinical validation of device?
• Why is clinical really the next necessary
step?
– Appropriate mitigation of potential risks?
– Appropriate enrollment criteria?
– Patients adequately informed?
– Sample size appropriate?

29. FDA’S PIVOTAL IDE REVIEW
 Focused on safety and plan for collecting and
evaluating study data
 Additional critical issues
– Trial endpoints
– Randomization, blinding, follow-up, etc
– Study conduct and monitoring
– Statistical analysis plan

30. BASIC SUBMISSION ELEMENTS
 Background of medical issue, the study goals, and
why this study will further the science
 Detailed description of the device under study
 Previous studies (preclinical and clinical)
– Summary of available data
– Why is a clinical study needed at this stage?
– What evidence supports the safety of this
study/device and the potential for the study data to
be meaningful?
– Are there outstanding safety questions that
should be addressed with preclinical data?

31.  Risk analysis
– What are the potential risks to the patient?
– Does the study mitigate the risks where
possible?
– Are the risks outweighed by the potential for
benefit and/or value of the study
 Patient monitoring and follow-up plan
 Inclusion and exclusion criteria
 Informed consent document
 Sample size and number of investigational centers,
with justification

32. SUBMISSION ELEMENTS, PIVOTAL IDES
 Primary and secondary endpoints
– Discussion of appropriateness of endpoint
parameters, hypotheses, and success criteria
 Basic trial design
– Controlled? If not, why not?
– Randomized? If not, why not?
– Blinded? If not, why not?

33. SUBMISSION ELEMENTS, PIVOTAL IDES
 Trial conduct and study monitoring
– Data handling and adjudication process
– Sponsor blinding
– Independent committees
– Case report forms
• Is the right information being gathered to
support the study endpoints and are investigators
adequately prompted to report adverse events?
 Provide enough detail to avoid ambiguity once the
trial has started.

34.  Statistical analysis plan
– Clearly defined S & E hypotheses
– Type-1 error and multiplicity
– Missing data handling
– Sample size calculations and assumptions
– Assessment of critical covariates
– Adaptive design plans
– Interim analyses and early stopping rules
– Data handling

35. PRIMARY ENDPOINT DESIGN
 Should evaluate the safety and effectiveness of the
device in the population expected to be indicated.
 Generally divided into
– 1 or more “safety” endpoints
– 1 or more “effectiveness” endpoints
 A study would be considered successful if both the
safety and effectiveness endpoints are met.

36.  • The clinical protocol should clearly and
prospectively detail:
– Methods for obtaining endpoint data
– Definitions for what will be counted as a
primary event in the analysis
– Situations in which patient data will be
excluded
– How missing data will be handled
– How the impact of covariates will be assessed

37. SAMPLE SIZE & FOLLOW-UP
 Driven by either:
– Primary safety endpoint
– Primary effectiveness endpoint
 Minimum number of patients and/or minimum
duration of follow-up may be required depending
on:
– Understanding of the safety and effectiveness
of the device
– Concerns regarding durability of device safety
or effectiveness

38. SECONDARY ENDPOINTS
 Generally used to evaluate additional meaningful
claims
 Generally only considered if primary endpoints are
successful
 Should be used to provide further insight into the
device effects and mechanisms of action
 Definitions and analysis methods should be clearly
detailed prospectively
 Not considered “statistically significant” unless a
pre-specified alpha allocation plan is in the protocol,
even if the p-value is < 0.05

39. FDA’S IDE REVIEW DECISIONS
 Approval
– Approves the trial for a specified number of
patients and investigational centers
 Approval with Conditions
– Allows sponsor to begin the trial if the sponsor
agrees to address the conditions (deficiencies) from
the conditional approval letter within 45 days
 Disapproval
– Trial may not start until sponsor addresses the
deficiencies from the letter, submits this information
to FDA, and receives approval

40. REVISION TO FD&C ACT, JULY 2012
 FDA shall not disapprove an IDE because:
• the investigation may not support a substantial
equivalence or de novo classification determination
or approval of a device;
• the investigation may not meet a requirement,
including a data requirement, relating to the
approval or clearance of a device; or an additional
or different investigation may be necessary to
support clearance or approval of the device.

41. RECENT REVISION TO FD&C ACT
 This means that an IDE cannot be disapproved on
the basis of FDA’s belief that the study design is
inadequate to support a future PMA, 510(k), HDE,
or de novo classification.

42. DOES STUDY FAILURE IMPLY PMA
DISAPPROVAL?
 Often but not always.
 PMA approval is based on a Benefit Risk
assessment
 FDA is always willing to review all available data to
determine whether there is a reasonable assurance
that the device is safe and effective.

43. DOES STUDY FAILURE IMPLY DEVICE
DISAPPROVAL?
 Alternatives
– Unexpected safety concerns are outweighed
by stronger than expected benefit
– Inconclusive study result is supplemented by
other clinical or non-clinical data
– Device is safe and effective for some limited
indication or patient population
 All of these alternatives may raise serious type-1
error concerns. FDA is therefore very conservative
in its consideration of these alternatives.

44. DOES STUDY SUCCESS IMPLY DEVICE
APPROVAL?
 Often but not always
 Sometimes the primary endpoints do not capture a
serious unexpected safety concern that is observed
in the trial.
 Other clinical or non-clinical data may conflict with
the study result.
 Can result in:
– Device disapproval
– Requirement for more data
– Limited indication

45. SOME GENERIC CASE EXAMPLES
 • LVADs
 • Pacemakers, ICDs, leads
 • Cardiac resynchronization
therapy
 • Ablation catheters and
generators
 • Cardiac monitoring devices
 • Heart valves
 • Stents
 • Cardiac occluders

46. EXAMPLE 1: NOVEL HEART FAILURE DEVICE
STUDY
 Novel implantable stimulation device to treat heart
failure
 Key characteristics
– Implant has serious risks
– Device is programmable
– Benefit may be symptomatic/functional
– Patients can feel the stimulation
 Previous data
– Feasibility data promising but single-arm

47. STUDY CONSIDERATIONS
 Safety
– Require long-term follow-up
– Safety success criteria should be rigorous to
balance symptomatic benefit
 Effectiveness
– Must be randomized to assess benefit
– Symptomatic/functional benefit requires blinding
– But how does one blind this study?

48. COMPANY PROPOSAL
 Implant device in all subjects
 Randomize to on vs. sham stimulation
 6-month follow-up, after which device may be
turned on or off in any subject
 Safety: all subjects pooled, compared to objective
performance criterion (OPC)
 Effectiveness: Responder’s analysis of quality of
life (QOL) and six minute walk distance

49. PROBLEMS WITH THIS PLAN
 6-month follow-up
– What if effect is short-lived?
– What if long-term safety concerns arise?
 Sham stimulation
– Is there enough data to know how to design true
sham?
– Will blinding truly be maintained?
 Safety
– Endpoint evaluates only procedure and presence of
the device, not effect of the therapy
 Effectiveness
– 6MW and QOL highly placebo sensitive
– Even if demonstrated, will benefit in these
endpoints result in appropriate risk-benefit?

50. FDA’S ADVICE
 12 month follow-up
 Multiple, rigorous safety endpoints
 If sham, more data needed to support
 More objective effectiveness endpoints
– Mortality/hospitalization composite
– VO2 max or ventilatory threshold
 Show reasonable risk-benefit profile

51. WHAT IS A COMBINATION PRODUCT?
 Safe Medical Device Act (1990)
 503(g)(1) Products that constitute a combination of
a drug, device or biologic
– Drug – Device
– Device – Biologic
– Biologic – Drug
– Drug – Device – Biologic
 Note: Drug – Drug, or Device - Device combination
not included here

52. REGULATORY COMPLEXITY
Product Pre market
framework
Approval FDA
Reviewing
centre
Quality
system
Safety
reporting
Device IDE PMA ,
510k
CDRH QSR MDR
Drug IND NDA CDER GMP AERS
Biologic IND BLA CBER or
CDER
GMP AERS

53. EXAMPLES
 Drug-eluting stent(DES) - CDRH
 Drug-eluting disc (oncology) - CDER
 Contact lens/glaucoma drug - CDER
 Spinal fusion device/therapeutic protein - CDRH
 Note : DES is a small metal mesh coil placed in a
blocked coronary artery . The metal is coated with
medicine and helps reopen the artery.
Drug eluting disk is considerd a drug
because it was designed to deliever chemotherapy
for brain tumors.

54.  Chemo drug/monoclonal antibody - CDER
 Scaffold seeded with autologous cells - CBER
 Interferon/Ribivarin therapy - CDER
 Embolization implant device/chemo drug - CDRH
 Vertebroplasty device/analgesic - CDRH

55. ESTABLISHMENT REGISTRATION FORM

56. DEVICE LISTING FORM

57. LINKS AND RESOURCES
 • FDA Center for Devices and Radiological Health
(CDRH) http://www.fda.gov/cdrh/index.html
 • FDA Office of Combination Products
http://www.fda.gov/oc/combination/
 • FDA US Agent
http://www.fda.gov/cdrh/usagent/index.html
 • FDA Establishment and Device Listing Forms
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/c
f RL/printforms.cfm

58. CUSTOM DEVICES
21 .C.F.R. 812.3(B)
 It is different from devices available
 It is not available to, or used by other MDs or dentists
 It is not available in finished form for purchase or
dispensing upon prescription
 It is not offered for commercial distribution through
labeling or advertising
 It is intended for use by an individual patient named in
the order form
 Made in a specific form for that patient or
 Made to meet the special needs of MD or dentist (i.e.
tool)
 http://www.fda.gov/downloads/RegulatoryInformation/Gu
idances/U CM127067.pdf

59. MEDICAL DEVICE RESEARCH
 Research Applications [ 21 .C.F.R. 812 ]
- Investigational Device Exemption (IDE)
- Approved by an IRB and, if applicable,
FDA
-Informed consent from all subjects
-Labeling for investigational use only
-Monitoring of the study
-Submission of required reports and
records
-Permits an unapproved device to be
shipped lawfully

60. DEVICE CLINICAL RESEARCH
 Significant risk (SR)
- IDE submission
 Non-Significant risk (NSR)
- Abbreviated requirements
 IDE exempt

61. SR VS. NSR DETERMINATION
 Decision based on use of device in study IDE
submission
 Sponsor makes initial assignment
 IRB makes determination
 FDA can disagree

62. SIGNIFICANT RISK
 Decision based on use of device in study
 IDE application
 Sponsor makes initial assignment
 IRB makes determination
 FDA can disagree

63. NSR DETERMINATION
 No IDE application to FDA
 Considered to have an IDE
 Abbreviated requirements only

64. ABBREVIATED REQUIREMENTS
 Labels device
 Obtains IRB approval
 SR vs. NSR determination
 Ensures informed consent
 IRB may waive documentation of consent if minimal
risk
 Monitors study
 Maintains records
 Makes reports
 Ensure CI maintains records and makes reports
 Refrains from promotion and other practices

65. ACCESS TO UNAPPROVED DEVICES
 Early/Expanded Access
-Emergency Use
-Compassionate Use
-Treatment Use
-Continued Access

66. EMERGENCY USE
 Life-threatening or serious condition with no
alternative
 Before or during an IDE
 FDA approval not required
 Report to the IRB within 5 days
 Report to the Sponsor and/or FDA
 http://www.fda.gov/ScienceResearch/SpecialTopics/
RunningClinical
Trials/GuidancesInformationSheetsandNotices/ucm
118823.htm

67. COMPASSIONATE USE
 Serious condition with no alternative
 Before or during an IDE study
 FDA approval required
 http://www.fda.gov/MedicalDevices/DeviceRegulati
onandGuidance/
HowtoMarketYourDevice/InvestigationalDeviceExe
mptionIDE/ucm0 51345.htm#continuedaccess

68. TREATMENT USE [ 21 C.F.R. 812.36 ]
 Life-threatening or serious disease
 No alternative
 Controlled clinical trial
 Sponsor pursuing marketing approval
 FDA approval required

69. CONTINUED ACCESS
 Public health need or
 Preliminary evidence that the device will be
effective with no significant safety concerns
 Occurs after the completion of the clinical trial
 FDA approval required
 http://www.fda.gov/MedicalDevices/DeviceRegulati
onandGuidance/
HowtoMarketYourDevice/InvestigationalDeviceExe
mptionIDE/ucm05 1345.htm#continuedaccess

70. TRIALS
 Regulatory Similarities in Trials
-FDA approval required before test articles can
be shipped
-IDE or IND
-FDA regulations specify sponsor and clinical
investigator responsibilities:
- 21 CFR 812 and CFR 312

71.  Regulatory Differences in Trials
-Contract Research Organizations (CRO)
1. Device regulations are silent about
them.
2.Drug regulations define transfer of
obligations to CRO.

72. ADVERSE EVENT DIFFERENCES IN TRIALS
DEVICES DRUGS
• 21 C.F.R. 812.150(a)(1) • 21 C.F.R. 312.32
• CI(clinical Investigator) report any
unanticipated adverse device
effects (UADE)
• CI report any adverse effects that
may reasonably be regarded as
caused by, or probably caused by,
the drug
• Sponsors report results of an
evaluation of a UADE to FDA and
all reviewing IRBs within 10
working days
• Sponsors notify FDA of any
unexpected fatal or life-threatening
event within 7 calendar days

73. MEDICAL DEVICE TRIALS
 Subject population usually in the 100s rather than
1000s
 No phases: Feasibility then pivotal study
 Blinding is less common
 “Controls” vary
 No placebo rather sham, active, historical
 CI training often critical (e.g. Human Factors)
 IRBs play a critical role

74. MEDICAL DEVICE CLINICAL TRIALS &
REGULATIONS IN INDIA

75.  A sleuth of reactive responses to judiciary and civil
society brought out notifications, circulars and
orders resulting in the downfall of clinical trial
approvals, with a peak of 500 approvals in 2010.
Realisation though slow, has led to reframing the
Drugs and Cosmetics Rules leading to Medical
Devices Rules, 2017 effective from January 1,
2018, for medical devices, including in vitro
diagnostic kits; New Drugs and Clinical Trials
Rules, 2019 effective from March 19, 2019; and
draft Cosmetics Rules, 2018 issued for public
opinion on November 29, 2018.[1]

76.  The Indian law that regulates the quality and safety
of medical devices has been amended and it will
now apply to all medical devices, effective April 1,
2020. Prior to the amendment, only 37 categories
of medical devices were regulated or were notified
to be regulated in near future in India.

77. THE IMMEDIATE CONSEQUENCE OF THE
AMENDMENT IN LAW IS AS FOLLOWS:
 Before October 1, 2021, all presently unregulated
medical devices will have to be registered by
respective importers or manufacturers with the
Drugs Controller General of India. However, those
medical devices which are already regulated or
have been notified to be regulated are exempted
from the requirement of registration
 Before August 11, 2022, importers, manufacturers,
distributors, whole sellers and retailers of presently
unregulated Class A (low-risk) and Class B (low-
medium risk) medical devices sold in India will have
to compulsorily obtain a license.

78.  Before August 11, 2023, importers and
manufacturers, distributors, whole sellers and
retailers of presently unregulated Class C
(medium-high risk) and Class D (high risk) medical
devices sold in India will have to compulsorily
obtain a license.
 In order to obtain registration for medical devices,
the importers and manufacturers of the medical
devices have to be certified as compliant with
ISO-13485 (Medical Devices – Quality
Management Systems – Requirements for
Regulatory Purposes)

79.  On February 11, 2020, the Government of India
gazetted two notifications – a new definition of
medical devices and The Medical Devices
(Amendment) Rules, 2020. The cumulative effect
of these two notifications is that all medical devices
will be brought under the fold of quality and safety
regulation from the effective date of both
notifications – April 1, 2020.

80. INDIA’S MEDICAL DEVICE QUALITY
REGULATION
 The standards of quality and safety of medical
devices are regulated in India by a law called The
Drugs and Cosmetics Act, 1940 (“DCA”). The
scope of DCA is restricted to only those medical
devices which are notified by the Government from
time to time as “drugs” (commonly referred to as
“notified medical devices”).
 The Medical Devices Rules, 2017 (“MDR”) have
been framed under DCA. These rules lay down
comprehensive quality requirements to be followed
by marketers/importers/manufacturers/sellers of
notified medical devices.

81.  The way DCA and MDR ensure the quality and
safety of notified medical devices at all levels of the
supply chain is by enforcing a mandatory license
requirement. All importers/manufacturers/sellers of
notified medical devices must obtain a license from
the appropriate licensing authority before
undertaking any commerce in notified medical
devices.

82.  A license is issued only after quality checks.
The license holder’s business premise is subject to
periodic inspection. A license holder is also
required to maintain detailed records of the sale-
purchase undertaken in relation to notified medical
devices and ensure traceability in the event of a
quality or safety-related failure or complaint.

83. THE MEDICAL DEVICE (AMENDMENT) RULES,
2020
 On February 11, 2020, the government also notified
The Medical Device (Amendment) Rules, 2020
(“MDR Amendment”). The MDR Amendment
introduces two changes to MDR. The first is the
introduction of a new chapter for registration of
Newly Notified Medical Devices by their
respective manufacturers and importers. The
second is an exemption for the 37 categories of
already regulated or notified medical devices
from the requirement of registration introduced by
the new chapter.

84. REQUIREMENT OF REGISTRATION
 The manufacturers or importers of Newly Notified
Medical Devices will be required to compulsorily
register their medical devices with the Drugs
Controller General of India (“DCGI”)
 It appears that the registration will be done
instantly after submission of all information and
documents on the online portal i.e., without any
examination of the information and documents
submitted by the applicant at the hands of DCGI.

85.  The registration process is relatively simpler and
should not be equated to a full-fledged marketing
registration or authorization. Any importer or
manufacturer of Newly Notified Medical Device will
be able to obtain registration on the submission of
the following information:
1.Name of the company or firm or any other
entity
2.Name and address of manufacturing site (for
devices manufactured in India only)
3.Specification and standards of medical
device (for imported devices only)

86. 4.Details of medical devices (Generic Name, Model
No., Intended Use, Class of Medical Device,
Material of Construction, Dimensions (if applicable),
Shelf Life, Sterile or Non-sterile status, Brand name
only if registered under India’s trademark law)
5.Certificate of compliance with respect to ISO 13485
standard accredited by National Accreditation
Board for Certification Bodies or International
Accreditation Forum in respect of such medical
device

87. 6.Free sale certificate from country of origin (for
imported devices only)
7.A duly signed undertaking stating that the
information furnished by the applicant is true and
authentic
8.The registration will be complete only upon
generation of a registration number.
9.Consequences of non-registration or of not
obtaining a license before the deadline

88.  If an importer or manufacturer of a Newly Notified
Medical Device fails to obtain a registration until
October 1, 2021, then it will have to cease import or
manufacture of said medical device until such time the
registration is obtained. It will be easy for the DCGI or
State-level Licensing Authority to know whether a
medical device is manufactured or imported without
registration. Under the Legal Metrology (Packaged
Commodity) Rules, 2011, every importer and
manufacturer of any medical device (whether regulated
or unregulated) is required to declare the date of
import of medical device or date of manufacture of
medical device on its label.

89.  Therefore, if a declaration exists on the label of a
medical device that the medical device has been
imported or manufactured on or after October 1,
2021, but the label does not show a DCGI
registration number, then it will be confiscated by
DCGI or appropriate State-level Licensing
Authorities and action will be taken against the
importer or manufacturer.

90.  Any violation of MDR including failure to obtain
registration or license before the stipulated deadline
may result in criminal prosecution resulting in
imprisonment and fine. Any stock of medical
devices that is sold without registration or license
could also be confiscated.

91. CLINICAL TRIALS FOR MEDICAL DEVICES:
 As per the National Ethical Guidelines, “a medical
device is a medical tool which does not achieve its
primary intended action in or on the human body by
pharmacological, immunological, or metabolic
means but which may be assisted in its intended
function by such means”

92.  Detection, diagnosis, prevention, monitoring;
 Treatment or alleviation of any physiological
condition or state of health, or illness;
 Replacement or modification or support of the
anatomy or congenital deformity;
 Supporting or sustaining life;
 Disinfection of medical devices; or
 Control of conception.

93. MEDICAL DEVICES, IVD’S ARE CLASSIFIED IN THE
FOLLOWING MANNER, ACCORDING TO THE RISKS
INVOLVED:
CLASS LEVEL OF
RISK
MEDICAL
DEVICES
In Vitro
Diagnostic
Products
A LOW Thermometers /
bandages /
tongue
depressors
Reagent
B Low –
Moderate
Hypodermic
needles/suction
equipment
IVD’s intended
to be used to
obtain test
results that are
not for the
determination of
a medically
critical status

94. CLASS
LEVEL OF
RISK
MEDICAL
DEVICES
IVDs
C Moderate-
high
Lung
ventilator/
bone fixation
plate
in detecting the presence of, or
exposure to, a sexually transmitted
agent; detecting the presence in
cerebrospinal fluid or blood of an
infectious agent with a risk of
limited propagation; or an
erroneous result that will cause
death or severe disability to the
individual or foetus; prenatal
screening of women for Rubella or
Toxoplasmosis
D High Heart valves
/ implantable
defibrillator
for detecting the presence of, or
exposure to, a transmissible agent
present is in blood, blood
component, blood derivative, cell,
tissue or checking for suitability of
organ transfusion or
transplantation

95. CLINICAL INVESTIGATION OF MEDICAL
DEVICES:
 Application to conduct a clinical investigation for
investigation medical device is to be made to the CLA
(CDSCO) via Form MD-22, by a sponsor, along with the
information specified in the Seventh Schedule (page
202). The CLA grants the permission to conduct a
clinical investigation for an investigational medical
device via Form MD-23 (Rule 52 of the Medical Devices
Rules, 2017)
 The fee for application to conduct a pilot or pivotal
clinical investigation is INR 100,000 and to conduct
clinical performance evaluation is INR 25,000. Per
rule 51(2), no fee shall be payable by any institute,
organisation, hospital-run or funded by Central or State
Government for the conduct of a clinical investigation.

96. Central Licensing Authority State Licensing Authority
The CLA, i.e., CDSCO is
responsible for enforcing the
Medical Devices Rules, 2017 for:
i. Import of all classes of medical
devices.
ii. Manufacture of classes C and D
iii. Clinical investigation and
approval of investigational medical
devices
iv. Clinical performance evaluation
and approval of new in vitro
diagnostic medical devices
v. Coordination with State
Licensing authorities
The State Drugs Controller is the
State Licensing Authority
responsible for enforcing the
Medical Devices Rules, 2017 for:
i. Manufacture for sale or
distribution of Class A or B medical
devices
ii. Sale, stock or exhibit or offer for
sale or distribution of medical
devices of all classes.

97. FOR CLINICAL INVESTIGATION OF AN
INVESTIGATIONAL MEDICAL DEVICE, ONE MUST:
 Obtain approval from the CLA.
 Obtain approval from a registered ethics committee.
 Register the trial with the Clinical Trials Registry of India
(CTRI), prospectively.
 Comply with The Medical Devices Rules, 2017published
by the CDSCO, Good Clinical Practice Guidelines,
published by the CDSCO, ethical principles described in
the National Ethical Guidelines for Biomedical and
Health Research Involving Human Participants, 2017
published by the ICMR.
 The enrolment of participants in the clinical investigation
must begin within a year of obtaining approval from the
CLA. Prior permission must be obtained from the CLA, if
the applicant is not able to initiate enrolment within the
prescribed timeframe.

98. CLINICAL PERFORMANCE EVALUATION OF NEW IN
VITRO DIAGNOSTIC MEDICAL DEVICES:
 Application to conduct a clinical performance
evaluation of new in vitro diagnostic medical device
is to be made to the CLA via Form MD-24, by the
sponsor, along with the applicable fee (specified in
the Second Schedule) and information (specified in
sub-rule 2 of Rule 59, page 159). If all requirements
are satisfactorily met, the CLA grants permission to
conduct clinical performance evaluation of new in
vitro diagnostic medical device via Form MD-25.

99.  The approval process for applications received
online via the SUGAM portal with respect to
medical devices can be accessed here. The Online
System for Medical Devices launched by CDSCO
allows an applicant to submit and track the status of
applications pertaining to medical devices.

100. NATIONAL ACCREDITATION BODY
 National Accreditation Board for Certification
Bodies (NABCB) under the Quality Council of India
set up by the Ministry of Commerce and Industry,
Government of India act as the national
accreditation body for the purposes of accrediting
Notified Bodies.
 NAB lays down the conformity assessment
activities for accreditation of Notified Bodies and
standards for such accreditation; prepare norms
and procedures for accreditation of Notified Body,
and audit a Notified Body periodically for assessing
conformance with the Medical Devices Rules.

101. NOTIFIED BODY
 For a fee, the Notified Body accredited by the NAB
audit the manufacturing sites to verify conformance
with the Quality Management System and other
applicable standards as specified in the rules. For
now, Intertek India, TUV Rhein land (Delhi), and
TUV Sud South Asia (Mumbai) are the Notified
Bodies registered for the purpose.

102.  Test license to manufacture for the purpose of
clinical investigation/ performance evaluation,
examination, demonstration or training
 Application shall be made in Form MD-12 for the
manufacture in small quantities for the purpose of
clinical investigation/ performance evaluation,
examination, demonstration or training. The fee for
Test License is INR 500.

103. IMPORT OF MEDICAL DEVICES
 An authorized agent in India having license to
manufacture or wholesale license for sale or
distribution for sale or distribution shall make an
application for grant of import license to CDSCO
through online portal in Form MD-14.
 For import or manufacture of medical device which
does not have predicate medical device, an
application for grant of permission for such medical
device after completion of its clinical investigation
under Chapter VII shall be made to the CLA in
Form MD-26 either by an authorized agent in case
of import or the manufacturer

104.  An application for grant of permission to import or
manufacture a new IVD may be made in Form MD-
28 either by an authorised agent in case of import
or the manufacturer.
 The fee for import of class A medical device per
site is USD 1000 and USD 50 per product; for
class B per site is USD 2000 and USD 1000 per
product, and for class C or D per site is USD 3000
and USD 1500 per product.
 The fee for import of class A or B IVD per site is
USD 1000 and USD 10 per distinct product, and for
class C or D per site is USD 3000 and USD 500 per
distinct product.

105.  Fee for import license for test, evaluation,
demonstration or training for each distinct medical
device is USD 100.
 The fee (and renewal) for manufacturing of class
A or B medical device per site is INR 5000 and INR
500 per product, and for class C or D per site is INR
50,000 and INR 1000 per product.
 The fee for permission to import or manufacture a
medical device that does not have its predicate
device is INR 50,000 and IVD is INR 25,000

106. POST-MARKETING
 The permission holder of Form MD-27 shall inform
the date of launch of a medical device in the market
to the CLA and shall submit Periodic Safety
Update Report from the date of launch in the
market and such report shall be submitted
every six months for first two years followed by
submission of the said report annually for the
two more successive years.

107.  The expansion of the definition of medical devices
and the requirement to obtain registration for
medical devices should not come as a surprise
because the Government had published a draft of
these notifications in October 2019.

108. FOLLOWING MEDICAL DEVICES HAVE BEEN
CONSIDERED AS DRUG BY DCGI
 Cardiac Stents
 Drug Eluting Stents
 Catheters
 Intra Ocular Lenses
 I.V. Cannulae
 Bone Cements
 Heart Valves
 Scalp Vein Set
 Orthopedic Implants
 Internal Prosthetic Replacements

109. REFERENCES :
 https://www.appliedclinicaltrialsonline.com/view/new
-regulations-medical-devices-india
 https://cdsatoolkit.thsti.in/regulatory-approval/
 https://arogyalegal.com/2020/article/all-medical-
devices-in-india-to-be-regulated-as-drugs-medical-
devices-amendment-rules-2020/