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Define medical device


A medical device is any instrument or apparatus for diagnosis, cure, treatment or prevention of diseases or conditions.

  • Not a drug or pharmaceutical agent


What type of devices does medical device cover?

Accessories – intended to be used with the device

In-vitro diagnostics – vials for samples

Custom-made devices – personalised device

Active medical devices – rely on source of power

Implantable medical devices – stay in human body



What are the two key European regulations that cover medical devices?

  • Medical Devices Regulation 2017/745
  • In vitro Medical Device Regulation 2017/746


Give examples of the 4 different classifications in EU regulation

  • I – corrective glasses and frames, walking aids, non-sterile dressings, stethoscopes
  • IIa – Devices to manage micro-environment of a wound short term corrective contact lenses, arterial blood filter, hearing, aids, antistatic tubing for anaesthesia
  • IIb – Insulin pens, contact lens solution, machines for haemodialysis
  • III – total hip and knee replacements, cardiovascular catheters, vascular stents


Why have a classification system? (I-III)

  • The greater the risk, the greater the reassurance that needs to be given
  • Manufacturers and their cost/controls – allows manufacturers which products to focus efforts on keep most sterilised.


What major changes were made to EU regulations in May 2017?

  • The Active Implantable Medical Devices Directive (AIMDD) & Medical Devices Directive (MDD) where combined to make the Medical Devices Regulation (MDR)
  • The IVD Directive (IVDD) was updated to In Vitro Medical Device Regulation (IVDR)


Explain the difference between the EU and US MD approval systems

  • EU has centralized and decentralized agencies throughout its member states
  • US the process is centralized through the FDA
  • EU system requires a lot more work for approval but is more flexible
  • US classification is easier to get but more rigid


What is the simple definition of a biomaterial?

A material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function in the body


List the different categories of materials in medical devices/implants:


  • Has no cells or living components


  • Implants with both cellular and materials components


  • Transplants
  • Can have a cost in terms of immune reaction



Give the simple definition of biocompatibility (in terms of bio-functionality)

The ability of a material to perform with an appropriate host response in a specific application

  • Appropriate host response: resistance to clotting, antibacterial
  • Specific application: hip joint replacement


Give the simple definition of biocompatibility (in terms of biosafety)

The exclusion of severe deleterious effects of a biomaterial on an organism

  • Includes cytotoxicity and mutagenicity, carcinogenity, pyrogenicity, irritation, etc.


Explain Polymethylmethacrylate, PMMA in making contact lenses

  • Used in rigid contact lenses: must be tough, stable and have excellent light transmittance
  • A hydrophobic, linear, amorphous polymer
  • One potential disadvantage is the lack of oxygen permeability
  • Melt processing, compression moulding and casting can be used.


Explain UltraHigh Molecular Weight PolyEthylene, UHMWPE

  • Used in low-friction inserts for bearing surfaces in Total Joint Arthroplasty
  • Must be tough, with a high impact strength and low coefficient of friction
  • Disadvantage: wear rate of 1mm/year


What are the different polymers that can be used in implants?

  • “Permanent”
  • Bioelimiable, i.e. excreted in urine
  • Bioresorbable/bioerodable i.e broken down by hydrolysis and metabolised



Describe PLA and PGA and explain their roles in allowing tuneable hydrolysis rates


  • Amorphous or semi-crystalline
  • High strength and thermoplastic properties


  • Very crystalline
  • Excellent mechanical properties


PLA/PGA copolymers have tuneable hydrolysis rates


Explain Hydrolysis

  • Water enters the polymer
  • A chemical reaction causes the bonds to break
  • Crosslinks cleaved – water soluble molecules
  • Side chains transformed/cleaved – water soluble
  • Backbone covalent bonds cleaved
  • This causes the pore size to increase – more water can enter
  • All polymers undergo some hydrolysis


What are the factors affecting hydrolysis reaction rate

  • Basic chemistry
  • Side chains
  • Crystallinity
  • Geometry
  • Porosity
  • Glass vs. rubbery state (rubbery means faster)



Explain Titanium-based Alloys in Femoral Implants

  • Lower moduli and ductility than steel
  • Allows load to be transferred to the femur
  • Improved tensile and yield strength
  • Improved corrosion resistance
  • Significantly lower density


Draw the pie chart showing the worldwide medical technology market by region


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What are trends in BRIC countries?

  • Rapidly growing wealth
  • More people getting insurance coverage
  • Improvements in healthcare infrastructure
  • Stable regulatory environments
  • Increased government healthcare schemes


What are trends shaping the sector?

  • Changing decisions makers
    • Physicians – hospital centralised procurement, patient advocacy groups
  • Influential new entities
    • Group Purchasing Organisation (GPOs)
    • Government-driven centralised bodies
  • Price pressure
    • National healthcare deficits
    • Aging population and increase in chronic diseases
  • Complex regulations
  • Commoditisation
    • With limited product differentiation, the threat of commodisation is high



What are the top 5 growth sectors worldwide?

  • Structural heart
  • Robotic assistance – da Vinci Surgical System
  • Infection control tools
    • Tools and systems to reduce HAI
  • Home care
    • Extending care outside of hospital walls
  • Neuro-devices
    • Implantable medical devices to treat brain disorders



What are the top 5 global technology trends?

  • Interoperability – integrating devices into a connected platform
  • Multi-Functional
    • Versatile systems > specialised equipment
  • Big Data
    • Captured health care data is expected to enhance “smart” functionality for diagnostic and treatment devices
  • Low-Cost Alternatives
    • Cost-containment initiatives are spurring innovation in medical technologies
  • Nanotechnology
    • Provides biocompatibility and functionality at a cellular level



Define Bioethics

Bioethics is the study of ethics applied to Biosystems

  • Concerns the moral, legal, political, and social issues raised by medicine, biomedical research, clinical care and life sciences technologies
  • Necessary because of the potential for human harm inherent in biomedical engineering


What are the three reports, codes, declarations that have shaped bioethics?


  • Established guidelines for human experimentation
  • Such as human voluntary consent is a must, which includes disclosure, capacity and voluntariness


  • WMA guidelines – not legally binding internationally
  • Forms the basis of most of the world’s ethical framework for medicine


Summarises ethical principles and guidelines for research involving human subjects

Three code principles identified:

  • Respect for persons
    • Choice of autonomous individuals be respected, people incapable of making their own choices are protected
  • Beneficence
    • Research gives favourable balance of potential benefits and harms
  • Justice
    • Researches must not exploit vulnerable people
    • Can’t exclude eligible candidates who may benefit without good reason


What are the new concepts included in MDD (93/42/EEC)?

  • Classification
  • Drug-device combinations
  • Performance
  • Criteria of acceptability
  • Risk assessment requirements
  • Clinical data requirements
  • Adverse event reporting and device monitoring in use



What are the steps required to get a medical device to market?

  1. Identify appropriate directive
  2. Determine classification
  3. Implement Quality Management System (ISO 13485)
  4. Technical report documenting compliance – Design dossier
  5. E.C. representative and include on label
  6. Audit by Notified Body
  7. Register with Competent Authority
  8. Prepare Declaration of Conformity. Affix the CE mark
  9. Audit by Notified Body annually.


Identify appropriate regulation

  • Need to identify which of the three EU medical device directives applies.
  • Is it IVD, Active device, implantable device?


Implement Quality Management System (ISO 13485)

  • A QMS is a formalised system that documents processes, procedures and responsibilities for achieving quality policies.
  • Regulations cover all the actions that the manufacturer does.
  • Most use ISO 13485: requirements for the design and manufacture of all medical devices
  • QS requirements result in GMP
    • Reduces number of non-conforming products
    • Continuous monitoring and corrective action requirements are interrelated to post-market surveillance


Technical Report documenting compliance (design dossier for class III)

  • Clinical evaluation is the assessment and analysis of clinical data to verify the clinical safety and performance of the device
  • An ongoing process throughout the life cycle of a medical device


EU: Performance

  • Defined as the action of a device with reference to its intended use when correctly applied
  • Performance doesn’t refer to the outcome, which may be influenced by other factors


US: Effectiveness

  • Defined as the extent to which a specific intervention, procedure, regimen or service, when deployed in the field, does what it is intended to do for a defined population.


Clinical evaluation data obtained through clinical investigation

  • Greater emphasis on this in new regulations
  • Trials are required if the device contains:
    • Novel technology, new materials, potentially hazardous technology


For class III, a design dossier must be produced

  • Very thorough, covering everything from design ® trials ® manufacture



Liaise with an E.C. authorised representative

  • They must be identified on the product labelling
  • Essential to have a legal representative within the EU in case of lawsuits


Audit by Notified Body

Designated bodies in member states for carrying out conformity assessment procedures

  • Auditing QMS
  • Examining design dossiers
  • Carrying out EC verification

Done by private enterprises – given permission to exist by competent body in a country

  • In US standardized by FDA


Register with Competent Authority

Responsible for recording and evaluating of incidents reported by the manufacturer

  • Responsible for monitoring and investigating malfunctions, deterioration and inadequacies


Prepare Declaration of Conformity, Affix CE Mark

  • CE marks indicate conformity to the relevant EU regulations and is ready for market


Annual Auditing by Notified Body

Ensures standards are being upheld


Describe the several challenges posed for Advanced Therapy Medicinal Products (ATMP) Regulation 2007

  1. A combination product’s Primary mode of action (PMOA) is often obscure
    1. This is means by which a product achieves its intended therapeutic effect or action
    2. Could be the therapeutic, pharmacological or mechanical action
  2. Variability of source materials makes it difficult to demonstrate a product’s homogeneity
  3. Small batch sizes and short shelf-lives make extensive testing impossible
  4. Randomized controlled clinical trials may not always be feasible
  5. Standards sometimes ill-defined
  6. The Directive leaves some discretionary powers to Member States to develop detailed procedures
    1. Could lead to discrepancies and to an uneven growth of this field across the EU


Give three examples of medical devices that the FDA criticised the EU for certifying.

PleuraSeal to seal lung incisions

  • Approved in the EU with minimal testing
  • Claimed to be superior to stitches in preventing air leaks and subsequent lung collapse
  • Withdrawn as US study showed cause 3x more leaks than stitches

Trilucent breat implants

  • Approved in EU without human testing
  • Soybean filler was found to break down into toxic compounds

Stent grafts to repair aortic aneurysms

  • FDA found put patients in severe risks – included blood clots, graft failure, and aneurysm rupture.


Explain why XenMatrix was sued

  • A surgical graft used in repairing abdominal walls during hernia repair
  • Discovered that batches had elevated endotoxin levels
  • As a result batches had to be recalled


List all the different physical sterilisation techniques

  • Physical Sterilisation Techniques
    • Steam
    • Radiation
    • X-ray radiation
    • E-beam radiation
    • Pulsed Light
  • Chemical Sterilisation techniques
    • Ethylene Oxide
    • Hydrogen Peroxide Gas Plasma



Describe the sterilisation technique steam and explain its advantages and disadvantages

  • Uses a high temperature steam, takes 20 minutes
  • Advantages:
    • Cheap
    • Good efficacy
    • Easy to control/monitor
    • Lack of toxic residue
    • Fast
  • Disadvantages:
    • High T,P
    • Distortion
    • May contain contaminants
    • Moisture absorption
    • Limits range of packaging materials


Describe the sterilisation technique Radiation and explain its advantages and disadvantages

Very Widely used, uses gamma radiation

  • Setup: Shielded in a pool of water, rack encapsulated in stainless steel rods
  • Advantages:
    • Complete product penetration
    • Can process in shipping package
    • No residue
    • Reliable, controlled, economical
  • Disadvantages:
    • Some plastics degrade
    • Discoloration of some products
    • Large capital outlay
    • Isotope containment
    • Can have ozone build-up


Describe the sterilisation technique Ethylene Oxide and explain its advantages and disadvantages

A clear, colourless liquid, toxic and a human carcinogen. Also flammable without an inerting compound

  • Products must be within gas permeable packaging
  • Sterilisation takes 2-16 hours
  • Advantages
    • Good efficacy
    • Can process in shipping package
    • Good compatibility
  • Disadvantages
    • Usually quarantined for 7-14 days
    • Many process variables
    • Residues
    • Increasing regulations (e.g. environmental)


List and explain the less established approaches

X-ray radiation

  • Excellent penetration, no ozone build up, machine generated radiation


E-beam radiation

  • No radioactive isotopes, no toxic waste, unsuitable for densely packed materials
  • Product heat


Pulsed Light

  • Pulse of intense light – which kills spores, bacteria, viruses and enzymes
  • Direct exposure required
  • Inexpensive


Hydrogen Peroxide Gas Plasma

  • Use hydrogen peroxide vapour in combination with plasma ® activity enhanced
  • Sterilises the surface only
  • Toxic so needs workplace monitoring


What are the key considerations in sterilisation processes?

  • Demonstrate efficacy
  • In compliance with standards or guidelines
  • Compatibility with a range of devices and materials
  • Capability of penetrating a range of loads, packing materials and device complexities
  • Safe for staff to use with minimal risks
  • Leaves no toxic residues
  • Rapid cycle time
  • Having a good environmental profile
  • Economical to acquire, use and maintain, easy to install
  • Methods available to monitor and confirm that the sterilisation process had adequately applied to a load.



Describe the Sterilisation Methodology

  • Determine the bioburden, i.e. the number of viable microorganisms on the product just prior to sterilisation
  • Take 10-30 samples ® wash into sterile “broth” – allow to grow ® count
  • Identify the SAL
  • Fractional-run sterilisation
    • Find the key kill rate per unit of exposure
    • Carry out a range of measurements and extrapolate


What is the Decimal Reduction Value (D-value)?

The time that a sterilisation process takes to inactivate a microorganism population of one logarithm, or 90%


The time that a sterilisation process takes to inactivate a microorganism population of one logarithm, or 90%

Validating sterilisation is a matter of process control, rather than finished product testing

Chemical Indicators

  • Colour changes – autoclave temperature/pressure reached for the required time
  • Dosimetry to detect ionising radiation


Biological indicators

  • Know population of bacterial spores on a paper or stainless steel disc
  • The spore type should be the most resistant organism for the process
  • Designed to show growth or no growth following incubation
    • Growth ® fail result
    • No Growth ® pass result