BN5208

Biomedical Quality and Regulatory Systems

Mrinal Kanti, PhD

Department of Biomedical Engineering
National University of Singapore

Email: biemkm@nus.edu.sg
Office: E1-05-24
My bio…

Ph.D: Biomedical Engineering; University of Texas Medical

School in San Antonio

Senior Research Scientist: New York State University

Medical School (SUNY), Brooklyn, NY

Consultant, Medical Affairs/Information, Johnson and

Johnson, APAC and ASEAN Regional office in Singapore

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 What this module is about:
In this module we will dive deep into regulatory and other
related aspects on medical devices.
Each lecture will have its own learning objectives and
outcomes as well as take home messages.

What this module is not about:

This module is not about pharmaceutical regulation…

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 Suggested Text Books/Readings

1. Handbook of Medical Device Regulatory Affairs in Asia

Author: Jack Wong.
Publisher: Taylor and Francis
2. Global marketing authorisation of biomaterials and medical devices
Author: Tobin JJ.
Publisher: Woodhead Publishing
Module’s Global Objectives:
In this module you will learn:
• Introduction to the regulatory profession
• Role of the regulatory professional
• Medical devices vs. Medicinals
• FDA classification of medical devices
• How medical devices are regulated in some countries including US, EU
and Singapore (we will also touch upon other countries)
• Medical device development process
• Approval of medical devices
• Quality system regulation and Quality management systems (QMS)
• Documentation and risk analysis of medical devices
• Commercialization of medical devices
• Ethics and medical devices
• Being in the shoes of a medical device regulatory professional

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 Learning Outcomes

After completing this module students should be able to:

1. Understand and analyse the medical device development process from design to post
market obligations
2. Comprehend the various risk-based classification strategies adopted in various
countries
3. Identify and understand the various 'Ethical' contexts as relevant to medical devices
4. Critique and discuss various case studies, including on safety, quality management
and post market obligations for medical devices
5. Demonstrate and evaluate the qualities needed to be a good medical device
regulatory professional

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Week Topics covered Comments
1 Introduction, what is and what is (not) a medical device, Role and characteristics of a Regulatory professional
2 Project discussion, FDA classification of medical devices, FDA classification of Tissue Engineered product Elearning through Zoom

3 Guest lecture by Industry expert Elearning through Zoom

4 Med device regulation in other jurisdictions (Singapore, EU)

5 Project management, Ethics in device regulations (case studies) Gp presentations 1-3

6 Conformity assessment, AI in medical devices Gp presentations 4-6

Recess week No lectures

7 Commercialization of medical devices, audits, Gp presentations 7-9

Post market obligations and processes; surveillance and vigilance
8 Quality system regulation, compliance and risk analysis and management, product recall Gp presentations 10-12

9 Medical device development process , Approval of medical devices, global regulatory strategy; Gp presentations 13-15

10 NUS well being day No lectures

11 CA Quiz (MCQs and open book)

12 Presentation

13 Presentation and Report submission (Please verify through Turnitin)

• Timetable subject to change

• Presentation topics will be disclosed the week before, thus all teams will have about the same amount of time to prepare. Gp
presentation to be 10-12 minutes.
• Teams would consist of 4 members, please choose your team members and we will finalize next lecture
• From now on lecture slides will be uploaded few days ahead of schedule so that you may do some self reading ahead of time
 100% CA, No final Exam…
This module is 100% Continuous Assessment (CA) for
ongoing formative learning
• Active class participation: 10%
• Peer assessment: 10% (to discourage non-contributing-peers and encourage
team learning)
• Post lecture discussions: 10% (including ethics case study discussions)
• CA quiz (open book): 40%
• Final report: 20 %
• Final project presentations: 10%

Teaching-learning format
• 1-1.5h of lecture followed by group presentations/case studies
• I will upload the topic few days in advance (latest by Tuesday), so that you have
sufficient time to prepare
• Absolutely NO memorization…but you must have the fundamental concepts
clear…hence all ears, eyes, brain (essentially all senses) during lecture and tutorials…
 Other housekeeping stuff…

Numerous avenues to ask questions and clarify doubts and

get instant feedback:
• During the lecture itself if you have a question on a particular slide being
discussed
• During the mid-lecture break
• After the lecture
• Through e-mails…
• Extra help and office consultations with appointment

Whenever I introduce a new term/word, I do define and explain it, but none-the-less
if you think you are not yet clear and want to discuss more, you are welcome to seek
further explanation…

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 At the end of this lecture
you should be able to:

• Define medical device

• Appreciate the wide variety of medical device
• Identify major sectors and top companies of the medical
device industry
• How they are different from pharmaceuticals/medical
products
• Define regulatory affairs
• Evolution of regulatory profession
• Define the scope of the profession, what medical device
regulators do…

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 Medical devices

Examples of some
common medical devices:
• Prosthetics
• Heart valves
• Cardiovascular stents
• Catheters
• Contact lenses

Just to name a few…

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Which of these are (not) medical devices…

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How can we make your cell phone a medical device…???

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Are bioreactors medical devices…???

But before that what

exactly is a bioreactor…

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 Definition
‘Medical device’ means any instrument, apparatus, machine, appliance,
implant, in vitro reagent or calibrator, software, material or other similar
or related article:

…. And

which does not achieve its primary intended action (function) in or on

the human body by pharmacological, immunological or metabolic means
…but which may be assisted in its intended function by such means

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…. specific purpose(s) of:

• diagnosis, prevention, monitoring, treatment or alleviation of disease or

compensation for an injury

• investigation, replacement, modification, or support of the anatomy or of

a physiological process, …

• supporting or sustaining life,

• disinfection of medical devices,

• providing information for medical or diagnostic purposes by means of in

vitro (IVD’s) examination of specimens derived from the human body

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 Top device companies
Company ~Market Cap ($B) Device type HQ location
262 Various New Brunswick, NJ
60 Various Chicago, IL
59 Various Minneapolis, US
30 Orthopedics Dublin, Ireland
36 Various Deerfield, IL
32 Surgery Dublin, Ireland
47 Diagnostics Waltham, MA

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Why regulate medical devices ?...The Billion
($$$) dollar question…

We regulatory medical devices to ensure:

1. Safety
2. Efficacy
3. Quality
4. Performance

Intended to safeguard the health and safety of:

• Patients
• Medical professionals
• Manufacturers

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 Medical devices go through a complex and long process
from conceptualization to marketing and thereafter either
for therapeutic or diagnostic use.

This module acts as a lexicon for medical devices and takes

you through a journey into their regulation and life cycles

• Med devices are significantly different from medicinals

• Combination products and are regulated through a
different and more complex pathway.

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 Rationale for Regulatory Guidance

• Consistent harmonised definition of term “medical

device” for use in global regulatory model
• Benefits to manufacturer, user, patient, regulatory
authorities
• Support global convergence of regulatory systems
• Eliminating differences allows patients earlier access to
new technologies and reduces costs of regulatory

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Medical Devices and Medicinals:
How do they differ?
 Mode of action defines and distinguishes a
medicinal/medical product and a medical device

• If the primary mode of action is pharmacological or

metabolic it is a medical/pharmaceutical product or a
drug and if the primary mode of action is by physical
means it is a medical device

Converging medical technologies: The distinction becomes more

complex and more important as “borderlines” become less distinct with
new technologies

Medical Medicinal
Device product/Drug

This gap is gradually decreasing with advent of new technologies… 22

Medical Devices
Product nature
Physical objects; complex components and
assemblages;
generally based on mechanical,
electrical, and materials engineering
Most act through physical interaction
with body or body part
Localised “site of action” treatment
effect
Duration and nature of exposure
varies widely
Typically durable; available for study
after use
Focus on biocompatibility of
materials
Relatively limited populations of
exposure
Not metabolized…
Medicinal/medicines
Pure molecules; based on
pharmacology and chemistry; now
encompassing biotechnology,
genetic engineering, etc.
Administered by mouth, skin, eyes,
lungs, or by injection; act through
metabolic, pharmacologic, or
immunologic means
Typically systemic effect
Short half-life in body
Consumed by use
Focus on systemic and local toxicity
Large populations of exposure
Most undergo ‘first pass’ mechanism
Medical Devices
Heterogeneous group; range from
tongue depressors to artificial hearts
Technologies, forms, and modes of
action very diverse
Industry composition
Over 80% small and medium sized
enterprises
Few “generic” devices
Intellectual property concerns
Continuous innovation and iterative
improvements based on new
science, new technology, and new
materials
Short product life cycle and
investment recovery period; little
patent linkage possible
Medicinal/medicines
Tend to differ only in molecular
structure, active site, and mode of
Application/action
Usually in forms of pills, solutions,
aerosols, or ointments
Very large multi-national companies
dominate
Significant “generics” industry
Extensive R&D of a specific
molecule; many years for new drug
to enter product pipeline
Intensive patent protection needed
due to long product life cycle
and long investment recovery period
Medical Devices
Product development
Invented and designed; often with
involvement of physician users
Designed to perform specific
functions
Regulatory approval on basis of
safety and performance
Constant iterative design and
process changes over product life
Short market life (~ 18-24 months)
Use and post-marketing
Most intended for professional use
Device malfunction
Use error
Adverse events most often local in
nature
Medicinal/medicines
Discovered in lab-based research
processes
Development by discovery and trial
Regulatory approval on basis of
safety and efficacy
Stable formulation
Long market life
Patient may choose to stop use
Drug interactions
Wrong drug or dose
Adverse events may be widespread
 In vitro diagnostic (IVD) medical
device
In Vitro Diagnostic (IVD) medical device’ means a medical device,
whether used alone or in combination, intended by the manufacturer
for the in-vitro examination of specimens derived from the human
body solely or principally to provide information for diagnostic,
monitoring or compatibility purposes”

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 In vitro diagnostic (IVD) medical
device

IVD medical devices include reagents, calibrators, control materials,

specimen receptacles, software, and related instruments or
apparatus or other articles and are used, for example, for the
following test purposes: diagnosis, aid to diagnosis, screening,
monitoring, predisposition, prognosis, prediction,
[or]determination of physiological status.”

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 What do regulatory professionals do…

• Play pivotal roles in all aspect of product development from

conceptualization, product lifecycle, clinical trials, to post approval and
even post marketing

• Keep track of ever evolving regulatory landscape

• Advisory on all legal and scientific aspect of the medical device including
collecting, collating and evaluating scientific data eventually leading to an
approved product ready for market

• At times the connecting link between various departments

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 Challenges for the Regulator

• Breadth of product offerings

– Impact of Specialization
– Keeping Up with Technology
• New burdensome regulations
– New Laws and the Downstream Impact on Hiring
Regulators (POLITICS!)

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 Challenges for the Regulator…

• Many masters
– From the inside (e.g. R&D, Mfg.), RA/QA = “The police”
– From the outside (e.g. the Regulators) , RA/QA = “The
crooks”
– From management, RA/QA = “What Do We Do Next?”,
“Delays”?
• Each device is different and requires a unique approach
• Released products don’t go away; need constant
revisions

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 The Regulated Component

• Integrate Regulatory Requirements early in the

Process!(talk to regulators early)
• Technical File = summary of design history and
evaluation
• Reporting
– Post Market Surveillance (PRO-ACTIVE vs RE-ACTIVE)
– Vigilance
– Field Safety Corrective Actions

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 The Regulated Component…

• Sales & The Customer

– Reimbursement
• Reporting to Competent Authority
– Complaints
– Feedback (different than Complaints!)
– Injuries (Vigilance)
– Recalls
• Marketplace Awareness

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 The Regulated: SME vs. MNC

• Unique personality for each

– SME: implementer, jack-of-all-trades
– MNC: “caretakers”, specialized
• As much on knowledge as it is on personality
and soft skills

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The Regulated: Life in MNCs

• System already established

• Role is as a caretaker
• Resources of a large department
• Likely single/few product lines
• Focus is on following a “recipe”
• Specialization

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 The Regulated: Life in SMEs

• Create Management Systems from scratch

• Often working alone and without a net
• Focus is on establishing a precedent
• Multi-disciplined; likely to have overlap with other
department(s)

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 … And Then, the Day-to-Day?
• Rely on your systems
– Personal
– Professional (e.g. networking)
– Organization
• Familiarization, never Memorization!
– Rely on the Supporting Documents
• Conservative Personality Traits
– Consider Impacts on Public Health (Ethics !)
– Consider Impact on Organization (profitability !)
• Aggressive Personality Traits
– New technologies
– Project Costs & Deadlines

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 Some take home points:
• Medical devices interact mechanically with a patient to affect a cure or
diagnose a condition
• Johnson and Johnson is the largest device company in terms of market
capitalization
• Lack in regulatory oversight may result in device failure and other ethical
and legal issues
• Safety, efficacy, quality and performance are critical consideration of
device success
• With advent of new technologies the distinction between medicinals and
medical devices are becoming more important
• Accessories are components of medical devices
• For a regulatory professional product and regulatory knowledge is as
important as personality and soft skills

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 References:
• https://www.fda.gov/

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