V3

▪ Cosmetic products (perfumes, shampoo, skin momisturizer…)

▪ Solid non-reusable units containing a medical product (Bottles, Blister packs)

▪ Personal protective equipment (protecive clothing, gloves, facemasks…)

▪ Human blood, blood products, plasma or blood cells (excluding blood derivatives)

▪ Transplants (Abdomen, tissues, cells of human origin or products with this content or origin)

▪ Medical products for exclusive use on animals

• MPG since 2. August 1994 until 2021

• MPG is the national realization of three european regulatories: RL 90/385/EWG – active implants, RL 93/42/EWG – medical products, RL 98/79/EG – In-vitro diagnostics

• Since 26. May 2021: step-by-step replacement of MPG with Medizinprodukterecht-Durchführungsgesetz (MPDG)

• MPDG is the national realization of the new EU-regulatory 2017/745, called Medical Device Regulation MDR (5. May 2017)

  • Change in regulations driven by the PIP-scandal (breast implant scandal)

  • Reorganization of the distribution of competencies between the federal government and the states

  • Central body responsible for regulating and implementing risk assessment measures

• Product scope expansion

• Implementation of uniquie device identification

• Rigorous post-amrket oversight

• Identification of person resonsible for regulatory compliance

• Common specificaitions

• Reclassification of devices according to risk, contact duration and invasiveness

• More rigorous clinical evidence for class III and implantable medical devices

• Systematic clinical evaluation of Class IIa and Class IIb madical devices

• No “grandfathering” porvisions

• non-active medical products (acting by gravity or operated by muscle power, Classification of medical products based on EU regulations → endoprosthesis

• active medical products ( devices powered by an external energy source, All devices highest risk classification → pacemaker)

• In-vitro diagnostics ( devices with a measurement function that can be active or non-active, classification rules based on the Global Harmonization Task Force System (A, B, C, D) → Blood glucose meter)

Scoping:

• Scoping for product idea

• More than 50% of ideas for medical products come from medical staff

Gate:

Can I…

• Successfully treat a disease with a medical product?

• Improve an existing procedure?

• Provide economic viability?

Investigation:

• Business case

• Medical indication

• Project planning

• Feasability analysis

Gate: Feasability -> Technical feasability given?

Developing:

• Prototype with manual

• Risk analysis and risk assessment

• Development of QPM

Gate: Classification ->> Risk Classification, Valid QPM?

• It must be ensured that the product fulfills its intended purpose and can be used safely for the benefit of the patient

• Any residual risk must always be less than the clinical benefit for the patient

• Unlike pharmaceutical law, medical device law protects not only the patient but also users and third parties → greater effort in the risk assessment of medical devices

-> Quality Management System

-> Instrument for identifying and meeting regulatory and customer demands

It‘s task is:

-> Planning - Documentation and description of stucture and process organizations

-> Implementation - Continuous optimization of processes

->Controlling - Determination of processes and resources to achieve desired results

…of all quality-related measures

• Companies that produce medical products are required to implement a Quality Management System (QMS) —> CE marking requirements

• Design of experimental studies, performance and monitoring of clinical trials

  • Good laboratory practice GLP

  • Good manufacturing practice GMP

  • Good clinical practice GCP

• GLP: regulates the processes and activities in the laboratory to ensure the reliability and safety of laboratory data

• GLP: protect scientific data integrity, and provide a clear and auditable record of open-ended research studies

• GMP: monitor the manufacturing processes to improve the quality, purity, and safety of products

• GMP: demonstrate whether individual batches of a regulated product are manufactured according to pre-defined manufacturing criteria

1. Get the facility design right from the start

2. Validate processes

3. Write good procedures and follow them

4. Identify who does what

5. Keep good records

6. Train and develop staff

7. Practice good hygiene

8. Maintain facilities and equipment

9. Build quality into the whole product lifecycle

10. Perform regular audits

• GCP: assure safety, reliability, and integrity of data reporting and methodology associated with clinical trials (Norm EN ISO 14155 and others for medical devices, ICH-Guidelines (International conference for harmonisation) for pharmaceuticals)

• GCP: ethical and scientific quality standard for designing, conducting, recording and reporting studies that involve the participation of human subjects

A group of standards has been published to ensure that the production of biomedical products is fit for their goals.

• ISO 9000:2015 focuses on QMS fundamentals and vocabulary and also provides a guidance for different kinds of organizations to promote quality management and productivity as well as address user requirements

• ISO 9001:2015 specifies QMS requirements as well as providing the standards for achieving user satisfaction

• ISO 15189:2012 defines requirements of competency and quality in medical laboratories

• ISO 17025:2017 focuses on the general requirements of calibration laboratories and competence of testing

• ISO 13485:2016 identifies the QMS requirements to provide medical devices

• ISO 14644:2019 focuses on cleanroom classification and associated controlled environments

• Specifications of the "Global Harmonisation Task Force” (STED = Summary TEchnical Documentation for Demonstrating Conformity to the Essential Principles of Safety and Performance of Medical Devices)

• All active implants must fulfill passive implants requirements while also ensuring safety and proper functioning of all its electrical parts

• Eg. Pacemaker • >100 regulatory standards • >100 company-specific standards

State of the art:

▪ Extracorporeal lung assistance (ECLA) only for temporary use

▪ Blood clotting due to dead zones caused by hollow fiber arrangement

Project at CVT:

▪ „3D-printed membrane architectures for ECLA application“

▪ Succesful fabrication of prous TPMS 3D membranes

▪ Aim: Optimized architecture to maximize gas exchange

▪ First implantable articficial lung will be tested in vitro, ex vivo and in vivo using new advanced animal model systems

Safety: Technical documentation

▪ Establishment of a quality management system

▪ Risk analysis and risk assessment. Biocompatibility assessment ➢ is the need worth the trouble?

▪ Which test have to be performed dependent on the risk class, the higher the risk the more extensive the regulations (e.g hip replacement)

Performance/Efficacy: Clinical documentation

▪ Clinical studies (for risk class III) approved by an ethics committee ➢ evaluation of clinical results

▪ The lower the class, the less „strict“ the tests

▪ Class III and II a/b are certified by indepented bodies

▪ Class I devices can be certified by the company itself

To demonstrate compliance with the regulatory product requirements for function, quality, safety and reliability, implant manufacturers must perform and document extensive device testing

-> Variety of ISO standards

Example: DIN EN ISO 21535 – Hip joint implant

▪ Definition of the Term „Hip joint implant“

▪ Intended function

▪ Design features

▪ Materials

▪ Design review

▪ Manufacturing

▪ Sterilization

▪ Packaging,

▪ Information disclosure

▪ Testing method

▪ Minimizing, analysing and evaluating residual product risks

▪ Ensuring biological compatibility, reduction or avoidance of infection risks

▪ Ensuring mechanical, electrical and electromagnetic product safety

▪ Testing and advice on compatibility with third-party products

▪ Examination of the product-related safety and instructions for use for completeness and comprehensibility

▪ Compliance with advertised product properties and specifications ▪ Guarantee of measurement accuracy

▪ Monitoring of the manufacturer and the medical product during the product life cycle

“In the context of medical devices, a clinical trial or a clinical investigation can be defined as any systematic investigation or study on one or more human subjects undertaken to assess the safety or performance of a medical device. Clinical trials for medical devices are predominantly conducted to identify the safety and performance of these devices in the treatment, prevention or diagnosis of disease.”

ISO 14155: Good Clinical Practice for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purpose.

➢ Protect the rights, safety and well-being of human subjects

➢ Ensure the scientific conduct of the clinical investigation and the credibility of the clinical investigation results

➢ Define the responsibilities of the sponsor and principal investigator

➢ Assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices

• §19 of the Medical device regulation (MDR) demands proof of their suitability for the medical use foreseen according to their intended purpose

• This proof includes the usefulness of the product for the patient when the product is professionally selected and used within the scope of its medical indication

• Legal requirements are proven with a certified QM system

▪ Conformity assessment procedure for medical devices is carried out by „Notified Bodies“

▪ Supervised by the government

▪ Audit and certify conformity assessment procedure of manufacturer

▪ For medical products: 13 in Germany, 62 in Europe ▪ TÜV, DEKRA, mdc,…

▪ European Commission sets concrete and strict criteria for the designation of approval bodies for medical devices in Europe