Medical Devices – US FDA Regulations Versus EU MDR

The EU MDR is a new addition to an already existing set of medical device regulations. Medical device manufacturers looking forward to implementing MDR must understand the changes that MDR brings with it. Moreover, they must also understand the critical differences between EU MDR and the US FDA, another renowned regulatory framework.

Differences between FDA Regulations and EU Regulations

Food and Drug Administration (FDA)

The documentation of US regulatory controls is according to the Federal Food, Drug, and Cosmetic Act along with the regulations in Title 21- Code of Federal Regulations (21 CFR) Parts 1-58, 800-1299. Medical device manufacturing companies have been using this framework to attain market authorization from FDA.

The basis of this regulation is the Title 21-CFR Quality System Regulations. These direct regulations manufacturers must fulfill requisites in regulatory steps in assessing the overall risk profile for each medical device. They should also ensure reasonable safety and effectiveness while sticking to the respective marketing pathways. These pathways are:

  • Premarket Notification (510(k))
  • Biologics License Application (BLA)
  • Exempt
  • Product Development Protocol (PDP)
  • Premarket Approval (PMA)   
  • De Novo Classification Request
  • Humanitarian Use Exemption

The EU MDR (Medical Device Regulations)

The EU MDR has replaced the existing Medical Device Directive (MDD) and the Active Implantable Medical Device Directive (AIMDD). It comprises a 28-pages long preamble, 10 chapters, and 16 Annexes. Each Annex contains multiple chapters that entail the following:

  • Obligations of the economic operators
  • Revised CE marketing procedure
  • Devices identification and traceability
  • Registration of devices and their economic operators
  • Clinical safety and performance summary
  • Development and rebuilding of the European data bank for medical devices

The EU MDR also presents primary responsibilities for the Notified Bodies about their role in clinical information processing to validate

  • The device’s intended purpose
  • The conformity assessments, and
  • The clinical investigations on the device

Another major role played by the EU MDR is to introduce

  • The post-market surveillance and vigilance of the marketed devices
  • Confidentiality and funding obligations, and
  • Penalties

MDR has also introduced the concept of coordination between member states, data protection, device registers, and Medical Device Coordination groups. Additionally, the Chapter X of EU MDR is concerned with Final Provisions, which are considered necessary by the EU to mitigate the devices already marketed.

FDA Regulations Versus EU MDR on Medical Devices

Classification of the Medical Devices

Classification Under FDA

Manufacturers who want to start the 510(k)-submission process must identify the suitable class of medical device using FDA’s medical device database. It is essential to know that the 510(k) pathway regulates devices belonging to Class I and Class II. These devices are of low and moderate risk. Under this pathway, manufacturers must present data for these classes of medical devices that demonstrate their functional equivalence with a previously approved device. This is also known as the predicate.

The Premarket Approval

The following products listed below do not have to follow the 501(k) pathway. Instead, they should follow the Premarket Approval:

  • Medical products that do not exceed limitations under 21 CFR 880.9
  • Medical products have a higher potential of causing an illness or an injury because of their application, such as implantable devices

According to Premarket Approval (PMA), sponsors present data that validate medical devices’ safety and effectiveness of data under evaluations of benefit versus risk. Sponsors must also show the device’s least environmental risk and higher life-sustaining potential.

FDA, PMA, and Class III Devices

According to the FDA, class III devices ‘support or sustain human life, are of substantial importance in preventing impairment of human health, or present a potential, unreasonable risk of illness or injury.’

For FDA, implementing general and special controls only is insufficient to prove the safety and effectiveness of these devices. Thus to obtain market approval, these devices also require a PMA application, as stated in section 515 of the Food, Drugs, and Cosmetics Act.

Classification Under EU MDR

Under the EU MDR, there are four categories of medical devices:

  • Non-invasive devices
  • Invasive medical devices
  • Active medical devices, and
  • A particular category has exceptions that include contraceptives, radiological diagnostic medical devices, and disinfectants

MDR also presents additional rules for medical devices employing nanomaterials. Overall, the MDR classifies devices based on risk, and this classification is as follows:

  • Class I – Non-sterile or without a measuring function (low-risk devices)
  • Class I – Sterile and/or with a measuring function (low/medium risk). MDR has also added reusable surgical instruments in this class
  • Class IIa (medium risk)
  • Class IIb (medium/high risk)
  • Class III (high risk)

There are different testing requirements for each device class. Furthermore, devices having preinstalled user handling software would be audited under MDR Article 6.11, Rule 11. Most software products are classified as Class I or IIb. Software used to monitor physiological parameters, such that the nature of variations in those physiological parameters can pose an immediate risk to the patient, is classified under Class IIb.

In contrast, software used for treatment or diagnostics with irreversible deterioration of the patient’s condition or death is classified under Class III.

Classification of Testing Processes

Testing Under FDA

Since most medical devices come under the 510 (k) process, clinical testing can take anywhere from 6 to 15 months. After the medical device manufacturer has accurately assigned a classification to the device, manufacturers can go under the process of 510(K) submission. Evaluations before submission include:

  • Preliminary safety testing
  • Risk estimation
  • Hazards identification
  • Hazards management planning
  • Risk mitigation strategy planning
  • Risk control analysis
  • Risk control effectiveness verification
  • Overall residual risk analysis
  • Risk vs. benefit analysis
  • Final risk management review

If the device fails to be classified, the manufacturer can apply the 510(g) protocol to the FDA. Under this process, the initial four months involve smaller study sizes, while the fifth step involves clinical trials of various studies. This way, the average timespan for the approval process can take between 7 to 14 months.

Testing under EU MDR

Under MDR, the device classification procedure occurs as follows:

  • Class I devices are evaluated according to Annex IV and V. Such devices are also exempted from conformity assessment for CE marketing by their Notified Bodies
  • Some medium-risk Class I devices and Class IIa devices may have to go through Conformity Assessments according to Annex XI, Part A
  • Class IIB and Class II devices must have strong technical documentation entailing Conformity Verification, Product Verification, and risk evaluation performed during the Conformity Assessments with NBs. This is based on articles from Annex II, X, and XI (Part A and Part B)
  • Those Class IIb and III devices that can be implanted must undergo further testing in special provisions
  • Experts must conduct assessments on devices with bioresorbable materials after receiving their reports from the NBs

Manufacturers looking forward to complying with MDR will also have to include reports on Common Specifications and Harmonized Standards. This implies that manufacturers will provide data to prove that their devices conform to the basic safety and performance requisites. These also include

  • A risk management system
  • Electrical safety, and
  • Mechanical security
  • Software life cycle processes (verification and validation, usable medical devices)

Furthermore, manufacturers must know that the Technical Documentation includes reporting the needs for future improvements in their active implantation devices.

Reach out for Compliance Support

If you are a medical device manufacturer looking forward to placing medical devices in the US or European markets, then TSQ&E can facilitate the process. We have a team of professionals who are well-competent in compliance matters both for MDR and FDA regulations. With the help of our compliance experts, you can fulfill all the required prerequisites and get your device placed successfully in these markets.

About the Author

Waqas Imam

S. M. Waqas Imam is associated with TS Quality as a Regional Partner. He is also an ambassador of Medical Device Community. He is an Industrial Engineer by qualification and served the manufacturing industry since 2011. He is also IRCA CQI Lead Auditor of ISO 9001 and other management system standards. He had served as Quality Assurance and Regulatory Affairs Manager in QSA Surgical Pvt. Ltd. and Ultimate Medical Products. He managed requirements of ISO 13485:2003, EU directives, CE marking and FDA. He also served as Expert Blog Writer for 13485Academy and wrote expert articles on various topics of ISO 13485:2016.