Navigating the regulatory process
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
What’s not covered
- Medical Device Directive
- Processes for the CAUK Mark or other territories outside of EU
- Details of the Quality Management System Requirements
- In vitro Diagnostics
- Drug Discovery
- Details of specific design and development process
What is covered
- Medical Device Regulations
- 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 device, in 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:
- Major
- Developing
- 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
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
- Submit Technical File to your assigned NB
- Review by Notified Body and/or Experts
- Questions Raised
- Onsite Audit
- CE Mark Applied
- 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
- Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use
- Standards, Training, Testing, Assessment and Certification | BSI (bsigroup.com)
- Approved bodies for medical devices - GOV.UK (www.gov.uk)
- ISO - International Organization for Standardization