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The design and development process - beyond ISO 13485:2016 and MDSAP?

Earlier this month, Rania Gerges, a Qserve Consultant and a QMS expert presented “Beyond MDSAP and ISO 13485: The Impact of the New EU Regulations on Audits”, in the International Track at the MedCon conference in Cincinnati, OH. Rania focused her talk on how the MDR impacts the design and development cycle. This blog summarizes the main points of her talk.

The new Medical Device Regulation (MDR, EU 2017/745) has introduced a number of new and significantly updated processes that must be integrated in a manufactures’ Quality Management System (QMS) if they currently or intend to sell medical devices in the EU. These processes go beyond the current requirements for ISO 13485:2016 and the Medical Device Single Audit Program (MDSAP). The table below provides a high-level comparison between the ISO 13485:2016 and the corresponding MDR requirements.

ISO 13485:2016

MDR

4.2 Documentation requirements

§  Technical Documentation – Annex II, III

§  Strategy for Regulatory Compliance – Article 10, Annex IX

§  Administrative Provisions – Annex IX

5. Management responsibility

§  Person Responsible for Regulatory Compliance – Article 15

7.3 Design and development

§  Strategy for Regulatory Compliance –  Article 10, Annex IX

§  Use of Harmonized Standards – Article 8

§  Common Specifications – Article 9

§  General Safety and Performance Requirements (GSPR) – Annex I

§  Clinical Evaluation – Article 61, Annex XIV Part A

§  Clinical Investigation –  Article 62-82, Annex XV

7.5.8 Identification

7.5.9 Traceability

§  Importers and Distributors Obligations –  Article 13, 14

§  Identification within the Supply Chain – Article 25

§  UDI System –  Article 27,  ANNEX VI Part C

§  Registration of Devices and Economic Operators – ANNEX VI Part A

8. Measurement, analysis and improvement

§  Post Market Surveillance – Article 83-86, Annex III

§  Vigilance and Trend Reporting – Article 87-89

§  Post Market Clinical Follow-up –  Annex XIV Part B

 

The basis for the new QMS requirements is laid down in Article 10 (General obligations of manufacturers) and Chapter 1: Quality Management System of ANNEX IX of the MDR. However, additional QMS requirements are scattered throughout the MDR articles and annexes. The MDR introduces additional requirements that go beyond Article 10, ISO 13485:2016 and the MDSAP. These requirements must be thoroughly reviewed to understand their interdependence and impact on key QMS processes.

 

A typical design and development process cycle includes a number of sequential design stages or phases as laid down by ISO 13485 or 21 CFR 820.30. These phases typically include Design and Development Planning, Inputs, Outputs, Verification and Validation, Commercialization, Post-Market and Design Changes. The MDR does not require any changes to the current design control structure with regard to having stages or phases. However, it is expected that the revised requirements in the MDR will be integrated in the design control cycle initiated during planning and carried throughout the design cycle, including the post market phase.

 

MDR Annex IX, 2.2 (c) states that “the procedures and techniques for monitoring, verifying, validating and controlling the design of the devices and the corresponding documentation as well as the data and records arising from those procedures and techniques shall specifically cover:  the strategy for regulatory compliance, including processes for identification of relevant legal requirements, qualification, classification, handling of equivalence, choice of and compliance with conformity assessment procedures”. Based on this requirement, the design and development process must not only consider the markets in which the device will be launched, compliance to industry and device specific regulations, and device classification, but also all the aspects needed to address the strategy for regulatory compliance. That being, device classification, as modified by Annex VIII of the MDR, and handling of equivalence, based on requirements in Part A of Annex XIV. These aspects will have regulatory implications and may also impact the product launch timelines.

 

Annex IX, 2.2(c) requires that “identification of applicable General Safety and Performance Requirements (GSPR) and solutions to fulfil those requirements, taking applicable Common Specifications and, where opted for, harmonized standards or other adequate solutions into account” to be covered as part of the design and development process. Many manufacturers fill out the Essential Requirements Checklist (Annex I) of the Medical Device Directive (MDD) just before technical file submission to apply for CE mark. This practice will change since Annex I (GSPRs) of the MDR has both significantly updated and completely new requirements that were not part of the MDD. The GSPRs along with the applicable Common Specifications and Harmonized Standards will impose new device requirements and specifications that must be addressed as part of the design and development inputs, outputs, verification and validations phases, not simply compiled for CE mark submission. To reference only a few of the significantly updated requirements in Annex I of the MDR, refer to GSPR 10.4 (Hazardous substances: CMR: carcinogenic, mutagenic or toxic to reproduction , endocrine disrupting substances), GSPR 12 (Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body), GSPR 17 (Electronic Programable Systems), GSPR 22 (Devices intended for use by lay persons) and GSPR 23 ( Label and instructions for use).

 

 

The clinical evaluation process laid down in the MEDDEV 2.7/1 Rev. 4, : A guide for manufacturers and notified bodies under directives 93/42/EEC and 90/385/EEC (published in June of 2016) requires the clinical evaluation process to begin during the development of a medical device. Premarket research and development are to be guided by clinical evaluation and risk management to define needs regarding clinical safety and clinical performance of the device. The process requires the manufacturer to evaluate if there are clinical data available, determine equivalence, define gaps in data for the device under evaluation, and determine whether clinical investigations are necessary to fill those gaps. Annex IX 2.2(c) of the MDR, requires that “the clinical evaluation, pursuant to Article 61 and Annex XIV, including post-market clinical follow-up,” be covered in the design and development process. From a documentation standpoint, the MDR adopts similar requirements of the MEDDEV 2.7/1 Rev. 4 with more specific contents to be included as part of the Clinical Evaluation Plan (CEP) and Clinical Evaluation Report (CER). In addition, requirements for biological equivalence mandate that materials used have similar release characteristics of substances, including degradation products and leachables. The MDR also introduces two new terms as part of the clinical evaluation documentation the “Clinical Development Plan” (CDP) and the “Summary of Safety and Clinical Performance” (SSCP). The SSCP is only applicable for Class III and implantable devices. Therefore, the design and development process must consider the handling of equivalence, potential needs for clinical investigation, as well as, planning and creation of the clinical evaluation documentation. The planning, gathering of pertinent data, and evaluation of data must take place throughout the design and development cycle and in the post market phases.

                                                                                                                                                                      

Another process that is interdependent to the design and development is Post Market Surveillance (PMS). PMS is not a new concept, but the MDR provides a clear definition for it in Article 2(60) and detailed requirements to be met in Article 83-86 and Annex III. Under the MDD and ISO 14971: Medical devices -- Application of risk management to medical devices, the planning for the Post Market Surveillance might be initiated after the device is placed on the market. Now as part of the MDR (Annex III), PMS now part of the technical documentation. Therefore, prior to receiving the CE mark and placing the device on the market under the MDR, manufacturer must create and plan the PMS including Post Market Clinical Follow-up (PMCF) activities documented in a PMS and PMCF plan to be executed once the device is placed on the market.

 

What does an MDR compliant design and development process look like? The table below summarizes the discussion above and gives additional design records that must be generated during the design development phases.

 

Design Phase

Design and development records required by MDR

Planning

§  Strategy for Regulatory Compliance

§  Clinical Development Plan (CDP)

§  Clinical Evaluation Plan (CEP)

Inputs

§  Applicable  General Safety and Performance Requirements (GSPRs)

§  Applicable Common Specifications

§  Applicable Harmonized Standards

Outputs

§  Specifications, procedures and techniques to conform to GSPRs

§  Labelling (label, sterile packaging label, implant card, IFU, website contents, etc.)

Verification and Validation

§  Design Verifications, Validations or other methods demonstrating conformity to GSPRs

  • Clinical Evaluation Report (CER)
  • Clinical Investigations, as applicable
  • SSCP (Class III and Implantable only)

Post Market

  • PMS Plan
  • PMS Report (Class I only)
  • Periodic Safety Update Report (PSUR)
  • PMCF Plan
  • PMCF Evaluation Report

 

 

Two common questions manufacturers typically ask: the first question being whether the technical documentation for legacy devices needs to be remediated. The answer is: Yes. The assumption is that manufacturers start with a blank page and document all the objective evidence to fulfill the requirements of Annex II and III to comply with the applicable General Safety and Performance Requirements (GSPRs). The second question is whether design control records such as the design history file (DHF) also need to be remediated. The answer is: Most likely, yes. During the remediation of the technical documentation and addressing the additional requirements of the GSPRs, it is likely the there will be new design inputs and subsequent outputs, validation and verification records, as applicable. Thus, impacting design records, and therefore must be captured as part of design changes to existing DHFs. In a best-case scenario, if the significantly revised or new GSPRs do not impose additional requirements to the device under remediation, the labeling (labels, IFUs) will certainly be updated as a result of GSPR 23.

 

Timelines are an important factor in all facets of any medical device manufacturer as they impact regulatory and business processes. Although Article 120 (Transitional provisions) does not require that the design and development process must be compliant by 26 May 2020, manufacturers must consider the additional requirements discussed above carefully with respect to forecasted launch dates and scheduling with their notified body for technical documentation review and on-site audits. Consequently, manufacturers may need to implement all the controls discussed above prior to 26 May 2020 to support the planning, implementation, and creation of the technical documentation for device CE mark under the new Medical Device Regulation EU 2017/745.

 

We hope with this blog, some of the manufacturers questions are answered. If you still have questions, please feel free to contact Qserve Group.

Rania Gerges
Post date: May 28, 2019
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