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Your idea for a medical device has been shown to potentially be commercially viable product, the next step is to prove your device is safe for the patient and user. In this section, Dr Toni Day, Experts in Residence at the University of Oxford, and Global Director of Quality and Regulatory Affairs at Organox, will take you on a journey through the CE Marking process to ensure you are prepared for the next step, design and development. Here we present a framework to help you navigating the regulatory process - led by Dr Toni Day, Experts in Residence at the University of Oxford, Global Director of Quality and Regulatory Affairs at Organox

NAVIGATING THE REGULATORY PROCESS 

 What’s not covered

  1. Medical Device Directive
  2. Processes for the CAUK Mark or other territories outside of EU
  3. Details of the Quality Management System Requirements
  4. In vitro Diagnostics
  5. Drug Discovery
  6. Details of specific design and development process

What is covered

  1. Medical Device Regulations
  2. CE Marking for Market Approval in the EU using a case study

Regulations - What are they?

Medical Device Regulations list out the obligations for those involved in design and development, manufacturing and supply of medical devices.

  • Safety requirements to ensure compliance
  • Emphasis on traceability throughout the whole supply chain
  • The requirement for clinical evidence
  • Rigorous vigilance reporting requirements, including reporting timescales, as well as requirements on what a manufacturer’s post-market surveillance system should comprise of.
  • Ensure Medical Device Safety for Patients.

In order to market medical devices in the EU, a CE mark certificate is required. This certification confirms that a product has met all regulations in place for medical devices.

What are the Medical Device Regulations?

  •  175 pages were published in the Official Journal of the European Union on 5 May 2017.

 Contains

  • 101 Recitals = the legal stuff
  • 123 Articles = what is required
  • 17 Annexes = how to do it

Why do we need regulations?

  • The medical device industry is heavily regulated.
  • Regulatory bodies — including the MHRA — have compliance regulations to make sure medical devices are safe to use.
  • These regulatory bodies also put an emphasis on creating quality products.
  • After all, producing quality medical devices is in everyone’s best interest.

What happens if you are not compliant ?

  • The PIP (Poly Implant Protheses) scandal broke out on March 29, 2010 when the AFSSAPS (the French health agency, now named ANSM) banned the sale and use of these silicone breast implants.
  • The health safety agency revealed that since 2001 PIP had been using an industrial silicone gel to fill these implants.
  • Since 2001, over 400,000 patients from 65 Countries had breast implants that were filled with a non-compliant industrial silicone gel.

* Jean-Claude Mas, the founder of PIP, was handed a four-year jail sentence and fined 75,000 euros in December.

 So far, what have we learnt?

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence. 

Step 1: what is the intended purpose?

 What is “intended Purpose”

  • The MDR defines the intended purpose in Article 2(12) as follows:
  • ‘Intended purpose’ means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation.
  • The manufacturer of a medical device is responsible for defining the intended purpose of that device.

 The Intended Purpose has far-reaching consequences:

  • It forms the basis of the decision whether or not a product is a medical devicein accordance with the definition of the regulation.
  • It will appear on all device documentation such as labels, instructions for use, and promotional or sales materials as well as the clinical evaluation.

Example: A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses. The Intended Purpose could be worded as "a system to detect the presence of [insert specific congenital defect] in the foetus".

But we would need more information:

  1. Major
  2. Developing
  3. Presence

Of note:

Annex XVI contains a list of devices without an intended medical purpose, which are nonetheless covered by the regulation.

Those devices are similar to medical devices in terms of functioning and risk profile, even though the manufacturers only claim non-medical purposes

For example – coloured contact lenses

 So far, what have we learnt?

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended purpose

Step 2: is it a medical device?

Medical Device under the regulations is:

  • Any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:
  • diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease.
  • diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
  • investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
  • providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations, and
  •  which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.

Example: A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses.

Definition Yes or No
means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes: Yes
diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease, Yes
 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, Yes
investigation, replacement or modification of the anatomy or of a physiological or pathological process or state, Yes
providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations, and Yes
which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on No
the human body, but which may be assisted in its function by such means. Yes

So far, what have we learnt?

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended purpose
  • Using the intended use it is a medical device

 

Step 3: what type of device is it?

 Categories of Medical Devices:

Category  Definition Examples

Non-invasive

Devices which do not enter the body

Plasters, walking sticks, wheelchairs, artificial kidneys (external dialysis)

Invasive

Devices inserted into the body’s orifices

Contact lenses, enemas, examination gloves

Surgically invasive

Devices used or inserted in surgery

Needles, scalpels, cardiovascular catheters

Active

Devices requiring an external source of power

X-ray equipment, ultrasound, TENS devices

 Implantable

Devices implanted into the body

Breast implants, orthopaedic implants, intraocular lenses

Example: a simple trans- cervical test, it can detect the presence of the major congenital defects found in developing foetuses.

 Duration of use:

 1.1.    ‘Transient’ means normally intended for continuous use for less than 60 minutes.

 1.2.    ‘Short term’ means normally intended for continuous use for between 60 minutes and 30 days.

1.3.    ‘Long term’ means normally intended for continuous use for more than 30 days.

So far, what have we learnt:

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended purpose
  • Using the intended use it is a medical device
  • Part of the device is invasive, part of the device is active

Step 4: what class of device is it? 

Application of the classification rules in Annex VIII to determine the risk class of the device.

The classification then determines the conformity assessment route for the device, including the amount of clinical data required to demonstrate conformity with the relevant safety and performance requirements.

There are 4 classes of general medical devices, determined by the inherent risk of a device. This risk assessment includes (but is not limited to) consideration of its intended length of use, its composition and whether it is implantable or active.

Classes of Medical Devices:

Class (Low to high) Examples
Class I

Wheelchairs, spectacles, stethoscopes, tongue depressors

Class lla

Dental fillings, surgical clamps, tracheotomy tubes

Class llb

Condoms, lung ventilators, bone fixation plates

Class lll

Pacemakers, heart valves, implanted cerebral stimulators

Class I devices are most non-invasive devices that do not interact with the human body and have the lowest risk. Class I actually contains several subclasses.

All Class I devices, including subclasses, make up about 70% of the market.

Class I Sub- Classes

Classification Definition Examples

Notified Body certification needed?

Basic Class I

Devices that are non-sterile or have no measuring function (low risk)

Wheelchair, plaster, hospital bed, bed pan

No – Self-Certification 

Class Is

Devices that are placed on the market in sterile condition

Personal protection kits

Yes

Class Im

Devices with a measuring function

Stethoscope, thermometer, weighing scale

Yes

Class Ir

A new subclass for products that are reprocessed or re-used

Surgical instruments and endoscope

Yes

 So far, we have learnt:

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended purpose
  • Using the intended use it is a medical device
  • Part of the device is invasive, part of the device is active
  • Device classification is due to device risk

Example of device classification: A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses.

  • Mechano-electrical sensor
  • Disposable tips
  • Detection software
  • Hardware

Example: a simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses disposable tip

  • Invasive device – Rules 5-8
  • Transient use (<60 minutes) - RulA simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses  hardware
  • Active device – Rules 9-13
  • Consider Rule 10
Re-consider the wording in rule 5

A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses – disposable tip

  • Invasive device – Rules 5-8
  • Transcient use (<60 minutes) - Rule 5

A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses software

Active device rules:

Disposable Tip Rule 5 Class IIa   

Hardware   Rule 10 Class IIa    

Software  Rule 11 Class IIa

 So far, what have we learnt:

  • If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence.
  • We have defined the intended purpose.
  • Using the intended use it is a medical device.
  • Part of the device is invasive, part of the device is active.
  • Device classification is due to device risk.
  • Devices can be combined or individual.

 Points to Consider

  • Animal material – design or manufacture
  • CNS
  • Central Cardiovascular system

  So far, what have we learnt:

  • If you are manufacturing a medical device, you must meet the obligations set out in the regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended use, user population and patient group
  • Using the intended use it is a medical device
  • Part of the device is invasive
  • Device classification is due to device risk
  • Devices can be combined or individual
  • Certain design and/or manufacturing process can increase the risk classification

Step 5: Conformity Assessment 

  1. Submit Technical File to your assigned NB
  2. Review by Notified Body and/or Experts
  3. Questions Raised
  4. Onsite Audit
  5. CE Mark Applied
  6. Post Market Surveillance/Vigilance

Technical File

The term technical documentation (or technical file) refers to all the documents that a medical device manufacturer has to submit.

The technical file is a requirement for the conformity assessment and, therefore, for the approval of medical devices.

Technical File Index

  • Device description and specification.
  • Reference to previous and similar generations of the device.
  • Information to be supplied by the manufacturer.
  • Design and manufacturing information.
  • General safety and performance requirements 
  • Benefit risk analysis and risk management 
  • Product verification and validation (Includes pre-clinical and clinical data)

 Testing should be guided by the General Safety and Performance Requirements

 Index for the technical documentation

 Standards are used to prepare test protocols. The risk management processes would be:

  • Hazard analysis
  • Risk evaluation 
  • Risk control and mitigation  

Example: A simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses.

  • Invasive
  • Pain
  • False positive
  • False negative
  • Sterilisation Failure
  • Tip dislodges

Clinical Evidence - Chapter VI Article 61 - 82

Example: a simple trans-cervical test, it can detect the presence of the major congenital defects found in developing foetuses.

 Disposable Tip:

  • Sterilisation Validation
  • Packaging
  • Shipping Conditions
  • Expiration date testing
  • Biocompatibility
  • Human Factors

Hardware:

  • Electrical safety Alarms
  • EMC
  • Biocompatibility
  • Human Factors

So far, what have we learnt?

  •  If you are manufacturing a medical device, you must meet the obligations set out in the Regulations.
  • Failing to meet the requirements could lead to a prison sentence
  • We have defined the intended use, user population and patient group
  • Using the intended use it is a medical device
  • Part of the device is invasive
  • Device classification is due to device risk
  • Devices can be combined or individual
  • Certain design and/or manufacturing process can increase the risk classification
  • A technical file is the evidence required for the CE Mark
  • The higher the risk class the more time and cost to get the CE Mark

 UKCA

  • The UKCA (UK Conformity Assessment) mark is the new UK product marking that will be required for certain products being placed on the market in Great Britain (England, Wales and Scotland). It covers most products that previously required the CE mark.
  • It will not be recognized in the EU market. Products that require CE marking will still need a CE marking to be sold in the EU.

*Remember if it isn't written down it didn't happen 

 Iterative and Multifactorial 

  • Technical 
  • Regulatory
  • Commercial

 Useful resources