Medical Device Design and Development Design Controls Andre Routh, PhD

Target Audience Design & Development engineers Quality Management System personnel Documentation Control personnel Regulatory Affairs professionals

Product Life-Cycle Market research Research Development Manufacturing engineering Manufacturing Distribution (sales & service) Product obsolescence and disposal

FDA Design Controls US regulatory requirement for Design Controls is found in 21 CFR 820.30: Code of Federal Regulations (CFR) Title 21 Part 820 Section 30 Design Controls

21 CFR 820.30 “All manufacturers (including specification developers) of Class II and III devices and select Class I devices are required to follow DESIGN CONTROLS [§820.30] during the development of their device.”

21 CFR 820.30 “The DESIGN CONTROL requirements are basic controls needed to ensure that the device being designed will perform as intended when produced for commercial distribution.”

Design Control: Definitions Product Result of a Process Specification Document stating Requirements Product Specification Document stating Requirements that results from Design and Development Control process Design and Development Set of processes that transforms Requirements into the Specification of a Product

21 CFR 820.30 Design Control Steps Design and Development Planning Design Input Design Output Design Review Design Verification Design Validation Design Transfer Design Changes Design History File

“Waterfall” Design Process

Overview of Design Control Planning Determine Customer Requirements D/D Planning Start of DC Process Design Input Design Planning Design Review Design Verification Design Validation Design Changes Outputs: Approved Product Specification, DHF, DMR, Batch record defined, Metrics, Documents, Records 10

Verification loop from Design Output to Design Input Two Feedback Loops Verification loop from Design Output to Design Input Validation loop that demonstrates that the medical device satisfies user needs

Feedback In practice, feedback operates at all levels. A change found necessary later in the process will have effects that ripple both backwards and forwards. Ripple Effects Analysis Regression Analysis

Verification and Validation Design Verification – Evidence that the manufacturer made the product right Design Validation – Evidence that the manufacturer made the right product

Design Reviews Design reviews are held at pre-defined points during the development process. Additional reviews will be held on an as-needed basis.

EU Medical Device Directives Medical devices for sale in Europe are regulated by “device directives” Medical Device Directive (MDD 93/42/EEC) Active Implantable Medical Device Directive (AIMDD 90/385/EEC) In Vitro Diagnostic Directive (IVDD 98/79/EEC).

EU Medical Device Directives Each directive includes a list of “Essential Requirements” (ERs) that must be satisfied before a device can be brought to market. One method of demonstrating conformity with the ERs is to use “Harmonized Standards”, which give the presumption of conformity with the ERs.

EU Harmonized Standards Medical Devices http://ec.europa.eu/enterprise/newapproach/standardization/harmstds/reflist/meddevic.html Active Implantables http://ec.europa.eu/enterprise/newapproach/standardization/harmstds/reflist/implmedd.html

EU Harmonized Standards Examples: ISO 13485 (QMS) EN 980 (Labelling) EN 10993 (Biological compatibility) EN 11607 (Packaging) EN 14155 (Clinical Evaluation) ISO 14971(Risk management) EN 60601 (Medical electrical equipment) See www.bsiamericas.com for a complete listing

QMS Standard ISO 13485 ISO 13485:2003 Medical devices — Quality management systems — Requirements for regulatory purposes ISO 13485:1996 Section 4.4 Design Controls. Intent very similar to that of 21 CFR 820.30

ISO13485 & 21 CFR 820.30 Design Control Guidance for Medical Device Manufacturers (March 11, 1997) “This Guidance relates to FDA 21 CFR 820.30 and Sub-clause 4.4 of ISO 9001”. NOTE: ISO 13485:1996 was the medical device version of ISO 9001:1994 to which the guidance refers.

Correspondence 1996 & 2003 1996 2003 1 Contract review 4.3.2, 4.4.4 7.2.1 2 D & D planning 4.4.2, 4.4.3 7.3.1 3 D & D inputs 4.4.4 7.2.1, 7.3.2 4 D & D outputs 4.4.5 7.3.3 5 D & D review 4.4.6 7.3.4 6 D & D verification 4.4.7 7.3.5 7 D & D validation 4.4.8 7.3.6 8 Control of D & D changes 4.4.9 7.3.7

Design Controls Comparison D&D Planning Design Input Design Output Design Review Design Verification Design Validation Design Transfer Design Changes Design History File D & D planning D & D inputs D & D outputs D & D review D & D verification D & D validation D & D changes

Design Dossier/ Technical File ISO 13485:2003 does not use the phrase “design history file”. However, Section 4.2.1 (f) states: “For each type or model of medical device, the organization shall establish and maintain a file either containing or identifying documents defining product specifications and quality management requirements.”

Design Dossier/ Technical File “These documents shall define the complete manufacturing process and, if applicable, installation and servicing.” NB-MED/2.5.1/Rec5 provides a good overall model for technical documentation

Risk Management ISO 13485:2003 21 CFR 820.30 Section 7.1, Planning for Product Realization requires that the manufacturer “establish documented requirements for risk management throughout product realization” Section 7.3.2, Design and Development Inputs requires that one of the inputs be the output of risk management. 21 CFR 820.30 Risk analysis is mentioned in in the Design Validation step.

Inputs to Design Control

Outputs From Design Control Design Control Outputs: Design History File, Design Master Record, Manufacturing information Batch record definition Feedback from the process Decisions on Outsourcing Post Market Surveillance on the particular product Metrics on performance of the process

Outputs From Design Control

7.1 Planning Product Realization The first step once a project has been agreed is to plan the product realization. This occurs before Design Control starts Planning should take as its input; resource requirements known; overview of the intended project [many times this will take the form of marketing data, competitive data, research information, or other sources which the organization wishes to pursue]; regulatory information

7.1 Planning Product Realization Planning includes consideration of any new processes needed for Product Realization. This could include production processes, as well as design control processes In planning, the following should be considered: Quality objectives and requirements for product Process and resource needs Verification, validation, monitoring, inspection and test activities, criteria for product acceptance Records needed

7.1 Planning Product Realization Risk Management shall have documented requirements established ‘throughout product realization’….In particular, this requirement does not limit the thinking process to Design Control, but invokes all the other requirements of Product Realization Risk Management shall be documented and records kept ISO 14971:2007 is recommended

7.2.1 Determination of Product Requirements The next step before Design Control is to determine the Product Requirements, basically the Product Specification. The organization shall determine: Requirements specified by the customer Requirements not stated by the customer but necessary for intended use Statutory and regulatory requirements…for the product

7.3.1 Design and Development The organization shall establish documented procedures…to plan and control the design of the product: Determine stages Design review, verification, validation and design transfer appropriate at each stage Responsibilities and authorities Planning output is a record, and shall be updated

7.3.2 D&D Inputs Functional, safety and performance requirements, according to intended use Regulatory requirements Post Marketing Surveillance (PMS) data, if available Risk management outputs are inputs to this stage The design input record must be documented and Approved

7.3.3 D&D Outputs Design Outputs must provide objective evidence the design inputs have been met Design outputs shall: be approved prior to release Provide information for purchasing and production Contain product acceptance criteria [production V&V]

7.3.3 D&D Outputs Design Outputs can include: Specifications for raw materials, component parts Drawings and parts lists Customer training materials Process and materials specs

7.3.3 D&D Outputs Finished medical devices specs Product and process software Quality assurance procedures Manufacturing and inspection procedures Work environment requirements Packaging and labeling specifications Identification and traceability requirements Regulatory authority submissions

7.3.4 D&D Review ‘At suitable stages’ – defined in Plan ‘systematic reviews’ ‘participants...shall be those…concerned…with the stage’ Key focus; the PRODUCT Key question; have we addressed all the REQUIREMENTS

7.3.4 D&D Review Design Reviews shall be conducted in accordance with the Design Plan Participants shall be competent to evaluate the stage [s] under review Records….and actions…shall be maintained: Purpose of review is to evaluate ability to meet requirements and identify problems and discuss and act as needed

7.3.5 D&D Verification Verification shall be performed in accordance with the Plan Purpose is to confirm that the Design Outputs [which have been documented and approved] have met the Design Inputs [which have been documented and approved]

7.3.5 D&D Verification Verification can include: Alternative calculations Comparing a new specification with proven spec Undertaking tests Reviewing documents prior to issue Records….and actions…shall be maintained

7.3.6 D&D Validation Validation shall be performed in accordance with the Plan Purpose is to confirm that the Product is capable of meeting the requirements for: The specified application The intended use

7.3.6 D&D Validation Validation shall be completed prior to delivery of the product Validation could include: Clinical evaluations required by regulations Real or simulated use conditions [completed device] Records….and actions…shall be maintained

7.3.7 Control of Change Design and development changes shall be identified and records maintained Changes shall be approved before implementation Changes shall consider evaluation of impact on product already delivered Records….and actions…shall be maintained

References 1 Code of Federal Regulations (CFR) Title 21, Part 820, Section 30 (21 CFR 820.30) Design Controls 2 ISO 13485:2003 Medical devices — Quality management systems — Requirements for regulatory purposes 3 ISO/TR 14969:2004 Medical devices — Quality management systems — Guidance on the application of ISO 13485:2003

References 4 Global Harmonization Task Force GHTF.SG3.N99-9 Design Control Guidance for Medical Device Manufacturers (June 29, 1999). Note 1: This document was archived on June 21, 2005 from the GHTF website because it is no longer the most current information available. ISO/TR 14969:2004, in which GHTF SG#3 participated, is considered to be the most current guidance. Note 2: This document contains the same basic information as Reference 5.

References 5 Design Control Guidance for Medical Device Manufacturers relating to FDA 21 CFR 820.30 and Sub-clause 4.4 of ISO 9001 (March 11, 1997) 6 ISO 13485:1996 Quality Systems - Medical devices — Particular requirements for the application of ISO 9001 7 GHTF web-site: www.GHTF.org 8 FDA CDRH web-site: www.fda.gov/cdrh

Contact André G. Routh, PhD Senior Product Expert BSI Product Services - Healthcare Email: andre.routh@bsi-global.com Phone/FAX: 609-654-1600 Cell: 571-239-0219