BN5208
Biomedical Quality and Regulatory Systems
Mrinal Kanti, PhD
Department of Biomedical Engineering
National University of Singapore
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
Although certain concepts are quite complicated, I will try my best to simplify it for your easy understanding.
The overarching intention is to ensure we ‘all’ are learning well and enjoying the journey at the same time
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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 Notes Instruction mode
1 Introduction, what is and what is (not) a medical device, Role and Face-to-Face (F2F)
characteristics of a Regulatory professional
2 Project discussion, FDA classification of medical devices, FDA classification F2F
of Tissue Engineered product
3 Med device regulation in other jurisdictions (Singapore, EU) F2F
4 Conformity assessment, AI in medical devices Group presentation 1-4 F2F
5 Project management, Ethics in device regulations (case studies) Group presentation 5-8 F2F
6 Salient features of devices, biocompatibility and design issues Group presentation 9-10 F2F
Recess week No lectures
7 Commercialization of medical devices, audits, Post market obligations and Blended Learning
processes; surveillance and vigilance (recorded)
8 Guest Lecture (pending confirmation) Blended Learning/Zoom
9 Quality system regulation, compliance and risk analysis and management, Group presentation 11-15 F2F
product recall, global regulatory strategy
10 CA Quiz (MCQs and closed book) F2F
11 Guest Lecture (pending confirmation) Blended Learning/Zoom
12 Project Final Presentations Gps 1-8 F2F
13 Project Final Presentations and Final report submission Gps 9-15 F2F
Schedule subject to change depending on availability of guest lecturers and travel needs
Other housekeeping info…
• Timetable subject to change
• Teams would consist of 6-7 members, please choose your team members
and self enrol in the gps indicated in Canvas
• Please make sure all team members are from same cohort
• 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
about 8-9 minutes (max).
• Each team may select 2-3 members to present, either for the post-lecture or
for the final presentation, ensuring everyone gets a chance to present
• Everyone would be involved in all relevant aspects of the presentation like
research, slides preparation, brainstorming, QnA etc
• From now on lecture slides will be uploaded few days ahead of schedule so
that you may do some self reading ahead of time
• For the weeks having blended learning approach, I will upload the lecture
recordings and also practice questions for self study
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100% CA, No final Exam…
This module is 100% Continuous Assessment (CA) for
ongoing formative learning
• Active class participation: 15%
• Peer assessment: 10% (to discourage non-contributing-peers and encourage
peer and team learning)
• CA quiz (closed book): 25%
• Final report: 25 %
• Final presentation(s): 25%
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 Wednesday), 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…
Name tag to identify students during in-class participation
Communication and active participation during lectures are integral components of
the learning process. To encourage such activities, please identify yourself while
asking questions (may place a name tag on your desk as appropriate) and this will
contribute towards the 15% in class participation component. Good communication/
presentation skills will help you immensely during your professional careers, from my
own experience in industry
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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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To help understand the needs of the cohort
better, let us begin by asking the following
relevant questions:
• Has anyone worked in a medical device manufacturing
company or as a medical device regulatory professional ?
• Why are we here, what we expect to learn from this
course?
• How it may help in my future endeavours or career
choices?
This cohort is very diverse with students from MSc, PhD (BME and other dept), some
working professionals as well as from other faculty like Dentistry participating. I will try
my best to create a good and conducive learning environment for everyone
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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 medical device manufacturers
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
Dynamic, may change every few years depending on the
market share, product constitution and profitability etc
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Why regulate medical devices ?...The Billion
($$$) dollar question…
We regulatory medical devices to ensure:
1. Safety
2. Performance
3. Quality
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… 25
Medical Devices Medicinal/medicines
Product nature Pure molecules; based on
Physical objects; complex components and pharmacology and chemistry; now
assemblages; encompassing biotechnology,
generally based on mechanical, genetic engineering, etc.
electrical, and materials engineering
Most act through physical interaction Administered by mouth, skin, eyes,
with body or body part lungs, or by injection; act through
metabolic, pharmacologic, or
immunologic means
Localised “site of action” treatment Typically systemic effect
effect
Duration and nature of exposure Short half-life in body
varies widely
Typically durable; available for study Consumed by use
after use
Focus on biocompatibility of Focus on systemic and local toxicity
materials
Relatively limited populations of Large populations of exposure
exposure
Not metabolized… Most undergo ‘first pass’ mechanism
Medical Devices Medicinal/medicines
Heterogeneous group; range from Tend to differ only in molecular
tongue depressors to artificial hearts structure, active site, and mode of
Application/action
Technologies, forms, and modes of Usually in forms of pills, solutions,
action very diverse aerosols, or ointments
Industry composition Very large multi-national companies
Over 80% small and medium sized dominate
enterprises
Few “generic” devices Significant “generics” industry
Intellectual property concerns Extensive R&D of a specific
Continuous innovation and iterative molecule; many years for new drug
improvements based on new to enter product pipeline
science, new technology, and new
materials
Short product life cycle and Intensive patent protection needed
investment recovery period due to long product life cycle
and long investment recovery period
Medical Devices Medicinal/medicines
Product development Discovered in lab-based research
Invented and designed; often with processes
involvement of physician users
Designed to perform specific Development by discovery and trial
functions
Regulatory approval on basis of Regulatory approval on basis of
safety and performance safety and efficacy
Constant iterative design and Stable formulation
process changes over product life
Short market life (~ 18-24 months) Long market life
Use and post-marketing Patient may choose to stop use
Most intended for professional use
Device malfunction Drug interactions
Use error Wrong drug or dose
Adverse events most often local in Adverse events may be widespread
nature
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/Medtronic are among 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
• For a regulatory professional product and regulatory knowledge is as
important as personality and soft/communication skills
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References:
• [Link]
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