BN5208

Biomedical Quality and Regulatory Systems

Steps in medical device approval

process, AI in MD’s and Conformity
assessment

Email: biemkm@nus.edu.sg
Office: E1-05-24
1
 Agenda: What we will learn today…
• House keeping items, midterm survey and individual group meet up
• Practice questions and case study
• Design attributes of medical devices: classic example of 3D printed hip implant
• Significance of individual components of total hip arthroplasty (THA) surgery
• Steps to approve and market a medical device: global picture
• Verification and validation of medical devices: why they are important
• The bumpy road to translation 
• Industry relevant case studies
• Medical devices involving Artificial Intelligence: Approval process
• Conformity assessment and its elements
• Take home messages

• The process of medical device development and regulation is much more complicated and is product
dependent.
• The intention of this module is to make complex and complicated concepts into bite sized chunks, thus
easier to comprehend and understand
 Housekeeping stuff: Midterm survey
Deadline to provide feedback is 25th, September, end of Recess week

Rationale:
• To ensure we all are having a good learning experience and any suggestion or
modification to further enhance the teaching-learning process
• Ensure module is industry relevant including sharing my own experience and
insights from Johnson and Johnson and also from talk by our expert from industry
(Mr Kia Moh Chu couple of weeks back)
• To ensure you are getting timely feedback and all relevant questions answered.
• Also the various case studies (ethics last week) and post lecture presentations are
providing independent and team-based learning and thus promoting critical
thinking and participation
 Housekeeping stuff: Individual group meet up
Groups Date, 23rd September, Time
1 11-11.15am

Rationale:
2 11.15-11.30am
3 11.30-11.45am
4 11.45-12noon
• To answer any questions you may have on
5 12-12.15pm
the project/report as well as on materials
6 12.45-1pm and contents covered thus far… All is fair
7 1-1.15pm game…
8 1.15-1.30pm
• Provide additional avenues for shy (not
9 1.30-1.45pm
10 1.45-2pm
so vocal) students who are unable to ask
11 2-2.15pm questions during regular lecture sessions
• If any group prefers a different day/time,
12 2.45-3pm
please let me know.
13 3-3.15pm
14 3.15-3.30pm
15 3.30-3.45pm
Practice questions and ethics
case scenario, ensure
continuous and ongoing
learning
 Practice question

A cardiovascular Heart Valve may belong to which FDA risk class of medical devices

1. Class I
2. Class II
3. Class III
4. In certain jurisdictions it is not considered a medical device
 Practice question

Which of the following doesnot come under the purview of regulatory agencies

1. Post market surveillance strategy

2. Clinical trial strategy
3. Product label
4. Marketing strategy and selling price
 Ethics case study for critical thinking and
brainstorming

An auditor from the country Kyrgiospos  arrived in Singapore to audit a

medical device manufacturing facility of company XYZ. Auditor was very well
received and after the auditing the ‘upper’ management took auditor for 5*
dinner with drinks and entertainment 
Q1: Is it ethical to provide this treatment to the auditor
Q2: Where to draw the line
Q3: Do companies usually have a budget for such expenses
Prosthetic device: classical example of medical implant

Significance of individual components in the success of the implant long term

Steps to market and approval: Bigger picture
Monitoring real world safety and performance…feedback
loop to design and development for future iterations

Preclinical
User need Design and Packaging Advertisemen Post-market Use and
Manufacture and clinical Approval
identification attributes and labelling and sales obligations disposal
trials

On market Postmarket
Premarket

Stage Premarket Placing on market Post market

Responsibility Manufacturer Manufacturer and regulator Manufacturer, regulator and end user

Attributes/activities Device attributes Labelling Surveillance/vigilance

• Safety and performance
• Assays and tests
Manufacturing
• Quality
• Packaging and
instructions for use
Approval
• Agency/ regulator
• Adverse events reporting
• Alerts and updates
• Monitoring safety and
performance
• Maintaining FAQ databases
• Training of clinicians and patients
(if needed)
 Design Verification and Validation process
Aka…waterfall diagram…

Verification: To ensure output is same as intended outcome, determined during input process
Validation: Conforms to user needs and thus address the intended unmet clinical needs of patient (part of clinical trials ?)
 The loo...…ng bumpy road to Translation…
Bench Bedside

IRB: Institutional Review Board

IACUC: Institutional Animal Care and Usage
Committee
 Topic to brainstorm

• With so many hurdles to regulation and other associated

activity that goes towards bringing a product to
market/patients, why still it makes sense to regulate medical
devices??
• What part do basic researchers and companies play in the
whole process? Why are they significant?
 Practice question
Identifying device response on users ‘under real world conditions’ is part of
which process

1. Validation
2. Verification
3. Medical device design input
4. Identifying user needs
Medical Devices involving AI

AI infused MD are increasingly being used in healthcare

 Advent of AI revolutionizes Healthcare

It performs four primary functions:

1. Enhances Automation process and thus decrease direct human intervention
significantly
2. Making complex tasks easier and potentially free from human derived bias and
subjectivity
3. Continuous and ongoing evolution with improvement of programs and algorithms
4. Better output and outcomes
 Risk based AI-MD classification

Although this is for local Singapore market, a similar strategy is applied by FDA as well as other regulatory agencies
Deployment of AI-MD’s
Interesting and invigorating Utube videos

https://youtu.be/jZg5QhL3Ckc (AI medical devices)

https://youtu.be/VAR44vnxWis (Medical innovations)

Is this a medical device, why? Why not?
Lets discourse and debate… shall we…

Lets identify the considerations:

• From a biocompatibility perspective

• From a regulators perspective
• From a manufacturers perspective

Hint: Define unmet medical needs?

 Conformity Assessment

“Conformity Assessment is the systematic examination of evidence

generated and procedures undertaken by the manufacturer, under
requirements established by the Regulatory Authority, to determine
that a medical device is safe and performs as intended by the
manufacturer and, therefore, conforms to the Essential Principles of
Safety and Performance for Medical Devices.”
 Components for conformity assessment
• Registration of personnel, devices and
Registration Device safety/performance manufacturing facility is fundamental to all
medical devices

1. Technical • Consistent product quality that conforms to

1. Registration of an established and accepted SOP
documentation
personnel
2. Declaration of
2. Registration of
devices
conformity (in • No deviation from established norm or
compliance of SOP) expectations

• Scope for improvement with advent of new

and improved technology

1. QMS: Quality • PMS to ensure it retains quality during the

management
system (Batch Quality product life cycle
consistency Management
/repeatability)
system • All documents need to be made available to
2. PMS: post-
market surveillance
regulatory body for verification
 Declaration of Conformity
• One element of a global regulatory model for medical devices is that the
manufacturer attests that its medical device complies fully with all applicable
Essential Principles for Safety and Performance and draws up a written
‘Declaration of Conformity’.
• The Product Owner or person authorised by product owner is responsible for
preparing the Declaration of Conformity

Essential Principles of Safety and Performance comprises of:

• General requirements of safety and performance that apply to ALL medical devices
• Design and manufacturing requirements of safety and performance, some of which
are relevant to each medical device
 Other important information
Adverse storage conditions and inefficient distribution practices may adversely
affect product quality and thus its overall performance and life span

The amount of technical documentation to be required will be influenced by

the potential risk class, class III > class II > class I

Onus lies on manufactured to adhere to the standards but subjected to

verification by regulatory agency (declaration of conformity or DoC,
manufacturer complies to all applicable “essential priinciples for safety and
performance”)
 References:
• HSA website
• Talk by Lin Anle, HSA
• RAPRo seminar, MDRA
 Lets learn together on the following Medical device
controversies

• Therac-25 (Group 4)
• HeartWare Ventricular Assist Device (HVAD) controversy (Group 5)
• The Pip implant scandal (Group 6)

10-12 minutes per group followed by QnA/discussion

Objective: To encourage individual and peer-to-peer learning which is typically followed in an industrial setting where small groups working
together come up a potential suggestion/brainstorm
Suggestions for expected deliverables/domains that may be covered

In your presentation you can discuss on issues like;

1. The background of this scandal
2. How and why it happened
3. What effect the scandal/controversy had on medical device regulations? Can
such occurrences be prevented in the future?
4. What role did the regulatory authority play in the controversy? Were there
any shortcomings on their part?
5. How was ethics compromised in your opinion?
6. Any other relevant/interesting findings from your research on the topic…