Implant failure:

Biomaterials and
design issues
 Schedule
Week Topics covered

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

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

4 Conformity assessment, AI in medical devices

5 Ethics in device regulations (case studies)

6 Implant failure: Biomaterials and design issues

Recess week

7 Commercialization of medical devices, audits, Post market obligations and processes; surveillance and
vigilance
8 Guest Lecture from Industry

9 Quality system regulation, compliance and risk analysis and management, product recall, global regulatory
strategy
10 CA Quiz (MCQs and closed book)

11 Independent and peer-to-peer learning

12 Project Final Presentations

13 Project Final Presentations and Final report submission

 Agenda for today’s interaction…

• Flipped classroom: Test our understanding by practicing

questions based on the video shared last week
• Use 3D-printed medical device prototypes to understand some
important and fundamental aspects of biomaterials used in
medical implants
• Understand and visualize why certain medical implants fail and
how engineers may address them
• Discuss relevant case studies on ‘Ethics and Professionalism’
based on my experience working for Johnson and Johnson, a
medical device manufacturing MNC

3
 Learning Outcomes relevant to
todays lecture

1. Comprehend the various risk-based medical device

classification
2. Identify and understand pertinent 'Ethical' contexts as
relevant to medical devices, using flipped-classroom strategy
3. Critique and discuss case studies relevant to medical
devices, using 3D printed medical device prototypes

4
Mid-term anonymous survey feedback:
Your voice matters

Comments that we can work on moving ahead:

• Sometimes you talk a bit fast, my first language is not English,
• The weekly practice questions before each lecture has enhanced my
learning and understanding, more practice questions please
• More real cases and stories from your life and when you worked for JnJ,
more insights into how ‘things’ happen in real industry
• Few students ask too many questions, sometimes disruptive
• The extra feedback session on 6th September was very helpful, more such
sessions please

5
 Flipped classroom strategy for
active learning

• Hope everyone has gone through the short video uploaded

last week.
• Now lets ensure we all have understood the concepts by doing
the practice questions based on flipped classroom concept
• Later, during discussion of the ethics cases, quickly form
groups of 2 members (person sitting right of you), I will pick
individuals at random to answer questions. This is to ensure
everyone are involved

6
Practice Questions to facilitate
understanding of previously
taught contents based on the
flipped classroom concept

7
Lets use a 3D-printed Medical Device
prototype (Hip Implant) to understand
some fundamental aspects of
biomaterials used, the rationale and
reasons for failure

8
 Need for suitable Biomaterials:
Hip prosthetic device
components (modular)

Ti alloy

UHMWPE
Co-Cr-Mo alloy

Musib M et al (2020). Going beyond PowerPoint: Using 3D printed medical device prototypes to promote ‘tactile’ and ‘visual’ learning.
Bone cement: Implant fixation

Polymethyl methacrylate
(PMMA)

10
https://www.sciencedirect.com/science/article/pii/S0268003312000721
Following ‘Blooms Taxonomy’ can we now apply the learnt knowledge and
analyse why only some parts of the implant are rough (while others are
smooth) and how it impacts the long-term performance of the implant

Smooth
surface

Rough
surface

Rough
surface

Hint: Think potential locations for osseointegration and locations involved in articulation (friction and wear)

• https://tips.uark.edu/using-blooms-taxonomy/
• Mazur E et al, (2004). Classroom demonstrations: Learning tools or entertainment? 11
12
Implant failure: causes and considerations

Implant debris phagocytosis, resulting in

wear-mediated osteolysis, eventually
leading to micro-motion, aseptic loosening
and implant failure

13
 Clinical Scenario (Application of the context)
Let us consider an actual clinical scenario faced by orthopaedic surgeons. We see two artificial
implants, the left being an artificial hip and the right being an artificial knee. These implants have
been in a particular patient for over 15 years. Recently the clinician had to take them out as the
patient complained of severe pain in the hip and knee region respectively. The X-ray shows
decreased bone density in the peri-prosthetic (?) region as shown by the arrows. In the inserts are
the retrieved acetabular cup (for the hip implant) and the tibial tray (for the knee implant) made
up of a polymer called ultra-high molecular weight polyethylene (UHMWPE) showing extensive
wear and delamination.

• Provide your reason as to why the density of bone around the peri-prosthetic region has
decreased
Can you now visualize the cascade of events that
transpire at the articulating surfaces of such
widely used (>5 million procedures/year)
implants and the rationale for usage of specific
biomaterials as individual components.

• In spite of these well-tested biomaterials,

some implants do fail eventually, necessitating
revision surgeries. Why are revision surgeries
complicated and to be averted?

Hint: Co-relate to phenomenon of osseointegration on the implant surface and

consequence of significant bone loss owing to revision surgery
15
 Practice questions to ensure
analysis and understanding of
the concepts just learnt

16
Medical device components consisting of biomaterials
are used to attain specific clinical outcomes which are
well defined and appropriately approved by relevant
authorities.

There may be ‘ethical issues and concerns’ during the

regulatory procedure that relates to how patients are
treated and non-approved usage of potential devices.

As a ethically upright regulator how would you address

such incidences

17
 Ethics case for critical thinking and brainstorming
(from my own professional career in JnJ)

You as the regulatory person in charge. Your team is going to

introduce a new medical device but you were just informed that
few of the clinicians involved in the clinical trials did ‘not obtain
patient consent’
• As an ethical regulator what would your suggestion to the upper
management and course of action?

Few other surgeons used the device for ‘off label’ purposes, but
were satisfied with the eventual outcome of the surgical procedure
• Would you encourage the surgeon to continue using the device for
off label usage as the results were satisfactory?

What is off label usage of medical device ?

 Ethics cartoon

Musib, M. (2019). ‘Creating and integrating relevant educational cartoons with scenario-based learning strategies to impart long-term ethics
learning’. 19
Now, lets look at the bigger
picture on the various steps in
the medical device regulatory
and approval process

20
Steps to medical device approval: Bigger picture
Monitoring real world safety and
performance… feedback loop to design
and development for future iterations

Premarket On market Postmarket

Prototyping Preclinical Use and

User need Design and Packaging Advertiseme Post-market
and and clinical Approval disposal
identification attributes manufacturing and labelling nt and sales obligations
trials

Initiation of Risk Verification Validation Surveillance/vigilance

identification and planning and QMS and Recall (if necessary)

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 • Packaging and • Adverse events reporting
• Assays and tests instructions for use • Alerts and updates
Manufacturing Approval • Monitoring safety and
• Quality • Agency/ regulator performance
• Maintaining FAQ databases
• Training of clinicians and patients
(if needed)
Lets take a 15 min break

22
 Quality System
Regulations (QSR) and
risk analysis and
mitigation
 What we will learn in this section

• Quality system regulations (QSR)

• Elements of QSR
• ISO 13485 and 21 CFR
• ISO 14971 and risk management
• What is risk and hazard
• Rubric for risk and hazard
• Estimation of risk and its mitigation/management
• Post market surveillance (PMS) and vigilance
• Proactive vs reactive strategies
• Complaint handling, reporting and CAPA
Quality System Regulations (QSR)
General consideration of QSR: ISO 13485

• Effective QMS (ISO 13485) is a key regulatory consideration for allowing

medical device manufacturers to market their products

• This International Standard specifies requirements for a QMS where an

organization needs to demonstrate its ability to provide medical devices and
related services that consistently meet customer and regulatory requirements

• Audit performed under the ISO 13485 may include an examination of a

product’s design and development

• ISO 13485 certification indicates that the processes for designing and
manufacturing specific medical devices produces consistent product quality
and safety.
Salient features of accepted quality standards
ISO 13485 21 CFR 820
Globally accepted standard and Imposed by FDA for US market
facilitates comply with general
regulatory requirements
It was derived from ISO 9001 and It is FDA-regulated good
moreso to make it more specific to manufacturing practices (GMP) for
medical devices medical devices
ISO 13485 is a voluntary standard Mandatory quality system regulation
(guidance document) and not a (QSR) for medical device distribution
compulsory structure/law for QMS in USA, but some flexibility is allowed
Fulfilment is called conformance Fulfilment is called compliance
Onus of Conformance to this standard Compliance is imposed by FDA on
lies with the company medical device manufacturers
FDA provided some input for its No influence by ISO on its
development development
 21 Code of Federal Regulation (CFR)
Title Vol. Chapter Part Regulatory entity
21 Food 1 I 1-99 FDA, Dept of Health and
and Drugs 2 100-169 Human Services

3 170-199
4 200-299
5 300-499
6 500-599
7 600-799
8 800-1299
9 II 1300-1399
III 1400-1499
 21 Code of Federal Regulation (CFR)
Part Specifics

800 GENERAL

801 LABELLING

806 CORRCTION AND REMOVAL REPORTS

807 REGISTRATION OF DEVICES AND ESTABLISHMENTS

Regulations 809 IVD

810 RECALL OF MEDICAL DEVICES

21 CFR; Parts 800-1050
- 800-861: Device requirements 812 INVESTIGATIONAL DEVICE EXEMPTION
- 862-1050: Device specific 814 PRE MARKET APPROVAL
requirements
820 QSR

821 MEDICAL DEVICE TRACKING

822 POST MARKET SURVEILLANCE

830 UNIQUE DEVICE IDENTIFICATION

860 MEDICAL DEVICE CLASSIFICATION

861 PERFORMANCE STANDARDS

 Quality System Regulation Key Elements

Complaint
Complaint Files
Handling

Design Transfer

Corrective and
Design Review Preventive Actions

Facility & Equipment

Design Controls
Controls

Quality System
Management Training
Record

Production and
Material Controls
Process Controls

Computer System
Records, Documents Validation
Procurement /Handling, Storage, and Change Controls
Distribution & Installation
Process
Validation

Key sub-systems/controls of QSR with Management at the helm/overall responsibility to ensure that all processes are followed
Risk management and
mitigation
 ISO 14971: Application of risk management
to medical devices
• ISO 14971 provides manufacturers with a framework to
manage the risks associated with the use of medical devices

• ISO 14971 specifies a process for a manufacturer to identify

the hazards associated with medical devices, to estimate and
evaluate the associated risks, to control these risks, and to
monitor the effectiveness of the controls.

• Risk management is the identification, assessment, prioritization and mitigation of risks

• Coordinated and economical application of resources to minimize, monitor, and control the probability and/or
impact of unfortunate events
• How they may be controlled (don’t confuse with removal of the risk)
• Assess risk/benefit ratio of risks that could not be reduced to an acceptable level
• Concept of residual risk and risk acceptability : Minimal risk that is acceptable to patients as part and parcel of
using a particular high risk medical device
 Concept of risk and Hazard
Hazard: Busy street
Event –
The ball rolls into Exposure P1
the busy street
Hazardous situation:
Small child playing
with a ball
P1 × P2
Harm P2

Harm: child is injured

Probability of
Severity of harm × occurrence of Risk
the harm
 Harm/hazard matrix

Severity/Pro Not likely Remote Occasional Frequent

bability
low Low Low Moderate High
moderate Low Moderate Moderate High
major Low Moderate High V. high
Severe (fatal) Moderate High V. high V. high

High and V high: not acceptable ;

Moderate risk: risk analysis and mitigation plan
Low risk: acceptable and approved
 Robust Practices for Risk Mitigation

Risk Mitigation

Proactive safety surveillance and Robust risk identification, Stringent post marketing
identifying new safety signals/ evaluation, characterization Adverse effect vigilance (PMV)
potential adverse-events and management reporting (AE)

Integrated approach
Inefficient documentation Noncompliant

Patient safety Reputation Litigation

Effective practices fundamental to risk management strategies

References:
RAPS.org
GC-MDRA program
FDA.gov