A. Introduction

Medical device design and development is a complex process with interdependencies. Development of medical devices encompasses a wide range of technologies to treat a variety of medical conditions. These therapies and equipment range from surgical tools to complex intravascular therapies and imagining technologies. Innovative products rely on well-characterized materials, novel biomaterials, or tissue engineering assembled together to solve customer needs. Product development is a process of evolving ideas into commercial products. Typically, about 55 -65 percent of new product launches fail. For every seven new product ideas four enter development, 1.5 are launched, and only one succeed (1). Product development standardization and guidelines help navigate through the steps to successfully develop products that can meet diverse product requirements.

Design control for medical devices provides a framework for developing an idea from concept through preclinical testing. This framework was initially implemented by the Food and Drug Administration (FDA) in 1990 to ensure medical devices were developed using a standardized method to insure patient safety. The Medical Devices Directive (MDD 93/42/EEC) similarly lists several requirements regarding the design of medical devices. International Standards Organization (ISO) 13485 is a voluntary standard that contains section 7.3 Design and Development recommending procedures that should be put in place by manufacturers in order to have a quality system that will comply with MDD 93/42/EEC. These design standards are important because they provide a methodical approach to developing new medical devices. Following the design process increases the chances that the true intent of the user need is transformed into the product that develops the intended device or therapy to the patient. The purpose of a methodical approach to device development is to provide a framework to systematically progress in a logical order that helps to minimize errors, reduce costs, shorten development time, and ultimately, develop a product that meets the customers intended use. It is a well-established fact that the cost to correct design errors is lower when errors are detected early in the design and development process (2).

The FDA created a design control guidance to ensure that device designers follow a procedure that insures the safety of the device (2). The process is structured to identify the product needs that are measureable and can be verified and validated to ensure safety, performance and dependability. The FDA design control guidance is intended to assist manufacturers in understanding quality system requirements concerning design controls. Assistance is provided by interpreting the language of the quality systems requirements and explaining the underlying concepts in practical terms. The design controls are an interrelated set of practices and procedures that are incorporated into the design and development process, i.e., a system of checks and balances. Design controls make systematic assessment of the design an integral part of development. As a result, deficiencies in design input requirements, and discrepancies between the proposed designs and requirements, are made evident and corrected earlier in the development process. Design controls increase the likelihood that the design transferred to production will translate into a device that is appropriate for its intended use (2).

B. Design Phases

A typical design process is shown in Fig. 1. The design process is applicable across all types of product development. The primary principles of the design process can be applied for devices, materials, biologics, etc. It is essential that a cross functional project team be assigned to the development project. This cross functional team typically consists of users, R&D engineers, quality assurance, regulatory, clinical, marketing and sales. A project schedule is critical to guide the team through the process, assign responsibility and ensure the project moves efficiently. A typical design process is comprised of a series of design phases. Each phase ends with a design review conducted by the design team. The design review is based on criteria defined by internal quality standards established within the company. The purpose of the design review is to ensure all activities in the previous phase have been satisfactory completed.

The intent of the design process is also to ensure that the appropriate customer requirements that were identified are met by the product requirements and performance and to reduce errors by making sure all steps are completed. Project design deliverables can be separated into five phases illustrated in Table 1.

Phase reviews allow the project team to review the results of the phase to make sure the project is meeting all design requirements. Project timeline and financial targets are also reviewed during the phase review. Corrections to the design can be identified early and corrected before proceeding. The typical model for the design process is referred to as the waterfall process illustrated in Fig. 2.

In the United States the Food and Drug Administration (FDA) requires that a Design History File (DHF) be created and maintained. Each manufacturer shall establish and maintain a design history file for each type of device. The design history file shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and requirement of this part (3). The DHF is a compilation of all the documentation created during the design process. The DHF would include phase review results, product specification and drawings, hazard and risk analysis project timelines, and test results.

C. Phase I: Concept Feasibility

The concept feasibility phase is the foundation of the product development process. This phase defines the product by identifying the user or customer needs. The customer needs identify the patient and the physician needs for a medical device. Ultimately, the product that is developed, not only needs to meet the product specification, but also must address the needs of the customer. To ensure this, the product specification requirements for a design are typically driven by the customer requirements documentation.

Several different tools exist to obtain customer feedback. The Voice of Customer is one common techniques used describe a method for capturing customer needs. Once identifying the customer needs, various techniques can be employed to define the relationship between customer desires and the product requirements. A planning matrix or House of Quality (4) can be utilized to relate what the customer wants to how a company that produces the product is going to meet those needs. The process relates what customer wants versus product features. The evaluation process should be completed cross functionally within organizations, especially between marketing, engineering and manufacturing.

After understanding the customer needs, a technique called brainstorming is used to generate multiple ideas to solve the problem the product is being developed for. This process generates a large number of possible solutions. The ideas are scored based on pre-defined criteria. Typically a cross functional team is used to generate and down select the ideas. The preferred ideas are selected and prototype engineering is used to develop the concept. During the prototype engineering phase several engineering tools are used to create and evaluate the concepts. Computer Aided Design (CAD) enables the engineer to create a computerized model of the product. The CAD model allows the product to be visualized to identify potential design problems. The use of computerize design software aids in creating virtual designed that can be evaluated for size, system interactions and assembly. Design problems that can be identified and solved virtually before making physical prototypes. Satisfactory designs are transformed in physical prototypes that allow the device to be evaluated for technical feasibility. These initial prototypes are evaluated for form, fit and function. Bench top testing of the prototypes is a method to evaluate functionality. Concept feasibility prototypes can also be used to obtain customer feedback. Evaluation matrices are a method to obtain numerical scoring and weighting of feature desirability. These scoring systems allow the different design prototypes to be measured against the customer needs and product specifications.

The goal of the concept feasibility phase is to obtain customer feedback, validate assumptions, demonstrate feasibility of key technologies and product functionality, address major identified risks, and develop a refined project. When evaluating the prototypes it is important to make sure that the product design is solving the actual design intent of the customer needs. At this point, design iterations can occur quickly, inexpensively and can provide rapid feedback. The initial prototypes are down selected to a few ideas that move into the design phase.

During the concept and feasibility phase it is important to understand the intellectual property of the ideas. A patent search is an important method to conduct to determine what ideas are protected. A patent mapping process is a method to identify potential competitors and patents. When a novel idea is identified it is important to insure the idea is protected before public disclosure of the idea. A freedom to operate analysis is another important assessment. Conducting a freedom to operate will make sure that the idea is not only patentable, but it can also be commercialized without infringing on other patents.

D. Phase II: Product Design and Development

Once the concept feasibility phase I review is successfully completed the engineering development can begin. This phase is typically the most complex and expensive phase in a project. It is important to have clear design specification inputs during this phase. Design specifications clearly state the requirements of the product. During the development phase the product team develops the product design and manufacturing processes based on detailed specifications and preliminary design documentation that are compiled to create the device master record (DMR). Engineering specifications for the product are developed for each component. Each component must fit into the overall product assembly. Material selection is also an important consideration. In addition to material performance, sterilization method and biocompatibility of materials should be considered. The design specifications should be clearly document and controlled as part of the design history record (DHF). Materials and components are fabricated based on the engineering specifications. Materials, components and sub-assemblies are assembled into the completed device. While evolving the design from the prototype to the product several design iterations take place. Shortening the design time for between iterations advances the project faster. Parallel development paths expedite evaluation of multiple design ideas simultaneously. The development phase should be a continuous loop of design, testing and obtaining customer feedback until all design requirements are met.

The design phase requires advance engineering tools, such as, finite element analysis and computational fluid modeling to help analyze material stress and strain or fluid flow properties. These types of analytical tools guide the design and help reduce errors before actually fabrication begins. During the design phase human factors should also be considered. A human factor analysis evaluates how the user will interface with the product.

From each component through final assembly, specific manufacturing methods must be considered. Design for manufacturing (DFM) is employed to ensure that the product design can actually be manufactured. Design for manufacturing is the general engineering method of designing products in a way that they are easy to manufacture. This design practice not only focuses on the design of a part, but also on the manufacturability. Most of the product lifecycle costs are committed at the design stage. The product design is not just based on good design, but it should be possible to produce by manufacturing as well. Often an otherwise good design is difficult or impossible to produce. During product design a manufacturing representative should be involved on the development team for input. Typically, the manufacturing engineer will identify the manufacturing processes and tolerances. Not including manufacturing in the design phase can result in additional design iterations, loss of manufacturing time, and overall resulting in longer time to market and higher costs.

An important part of the design process is to evaluate the safety and risks. During product development several techniques are employed to improve product safety and reduce hazards to the patient. A hazard or risk analysis is a methodical approach to identify and analyze potential hazards to the patient. The risk analysis is required by the FDA and is typically conducted during the development phase (5). Identification of potential product conditions that could cause harm to the patient is the main reason for conducting a risk analysis by of the product.

Hazard Analysis (HA) and Failure Mode and Effects Analysis (FMEA) are two tools used to evaluate the risk associated with the development of medical devices. The hazard analysis is a “top-down” approach while FMEA is a “bottoms-up” approach. Typically the hazard analysis is conducted early in the design process and the FMEA is conducted when the design specifications are more defined. Both risk analysis are updated throughout the design process.

A hazard analysis is a qualitative examination of the device from the user perspective. Device interactions with the patient are considered. Internal design elements of the device that could cause the failure are ignored in the hazard analysis.

FMEA is a qualitative examination of the individual components of the device. Conducting the FMEA considers how each component might fail, how probable the risk of component failure is (occurrence) and the effect of each failure on system operation. Failure of a component inside a subassembly of the product has the potential to affect the patient. Conducting the FMEA evaluates the severity of these failures to the patient. If the FMEA risk is identified as high (high occurrence and severity) a solution and/or appropriate design controls must be implemented to protect the patient.

The hazard analysis and the FMEA are complementary to each other and together create a comprehensive risk management program. Both risk analysis tools should be documented, approved and controlled. These documents are required by the FDA design control process and should be part of the DHF. Thorough risk analysis plans, with mitigation of sever risks, will identify that patient benefits out way patient risks and improve FDA approval. When changes to the product occur these documents should be reviewed to make sure the risk have not been effected by the design change.

After the product is designed, design evaluation of the product can be performed. Each design specification must be able to be tested to insure the output meets the input. This is a critical step in the design process. First, this process allows product performance to be evaluated. By evaluating the product throughout the design process minimize design deficiencies that can be corrected early in the design process to reduce cost.

E. Phase III: Design Verification

Verification tests measure features and dimensional specifications that are fully verifiable on the product through a physical measurement. Design verification is done by checking if the design meets its intended product requirements. In addition to the internal standards defined by the quality standards of the company and the customer requirement documentation, design verification also needs to account for regulatory requirements. New products are subjected to ISO and FDA regulatory safety requirements that need to be tested either as part of design verification or validation efforts.

Once the design is evaluated and it is probable that all the design inputs can be met the design freeze occurs. A design freeze implies that no additional changes are made to the product so that the verification and validation of the product can be completed. Design freeze should not occur until all team members are completely satisfied and agree that the product design meets the intended use. It is easier and less costly to iterate the design prior to design freeze.

After design freeze, the actual product is manufactured. Products manufactured for prototypes using alternative processes may not be representative of the actual product. The product manufactured for verification testing should be built using the actual manufacturing processes so the product is representative of the final devices. A verification test plan is created to identify the test material and methods. The verification plan should also describe the statistical methods to determine sample size. Critical items identified in the risk analysis should drive the verification. Design verification is the testing required to determine whether the design outputs meet the design inputs (5). A useful method is to create a table identifying the design inputs, test methods and design outputs. Results of all testing is documented in the verification test report. These documents are an important part of the DHF.

F. Phase IV: Product Validation

Product design validation is the process of examining the product to provide objective evidence of the product requirements, if they are verifiable, and if they meet the product specification and intended use. This would include fatigue strength, life cycle testing, and processes, such as, package seal strength, sterilization, and transportation testing. Shelf life of the product is also determined during this phase. Shelf life can be tested using accelerated and real time aged product, including the packaging materials, followed by product testing. External standards typically outline the test requirements. When conducting a validation it is important to use products that are representative of finished devices, manufactured by actual manufacturing methods and are traceable to certified materials. Protocols should be written that specify testing methods, define the acceptance criteria, and justify sample size criteria.

G. Phase V: Design Transfer

Design transfer refers to transferring the design to manufacturing for commercial use. In this phase the design documents are released to production. The Device Master Record (DMR) contains specifications for building the product. The Bill of Materials (BOM) is a list of the materials required to build the product. Manufacturing typically involves both internal and external suppliers. Internally, manufacturing processes are required to be documented. Quality assurance programs are implemented to ensure product specifications are consistently met. Process validation activities also need to test for design performance (validation) at the manufacturing tolerance levels. Typically, design validation activities are conducted using samples obtained from nominal manufacturing processes. Hence, process validation activities need to account for manufacturing tolerance effects on design performances.

• When transferring to external suppliers it is essential to select suppliers with capabilities to consistently produce the product to specification. Five success factors were defined by Caldwell et al (6).
• Define success: All stakeholders within an organization must agree on the meaning of success. Appropriate investment up front that defines clear success metrics is critical to ensure success in outsourcing design and implementation.
• Transition effectively: There are two parts to ensuring smooth transition. First, the current operations must proceed uninterrupted; second, there must be a parallel initiative to transfer seamlessly to outsource operations.
• Strengthen Coordination: Once an outsource relationship has started, it requires ongoing coordination to sustain operational excellence. Project management tools, such as, operational calendars and dashboards can be extremely effective.
• Retain Flexible: There are two approaches to accommodate flexibility. First implementing flexible systems and secondly instituting a change control process for adapting to unanticipated changes.
• Strive for improvement: long term outsourcing success requires a process for ensuring continuous improvements and corrective action.

H. Conclusion

After design transfer is completed the product is released for commercial use. A post mortem of the design process can reveal improvements for future product designs. Post market analysis of the product provides early detection of issues and important information for product enhancements. Monitoring of device failures is important for product field improvements. Corrective actions can be assigned to revise important design oversights. These activities are part of the product development lifecycle and process continuum.

References

1. Cooper, Robert G., Winning at New Products, Addison-Wesley Publishing Company, Inc. 1993.
2. FDA U.S. Food and Drug Administration. Design control guidance for medical device manufacturers. This guidance relates to the FDA 21 CFR 820.30 and Sub-clause 4.4 of ISO 9001. March 11, 1997.
3. Trautman, Kimberly A., The FDA and The Worldwide Quality System Requirements Guidebook for Medical Devices, America Society for Quality Control, Milwaukee, Wisconsin 1997.
4. Hauser, JR and Clausing D. The House of Quality. 1988.
5. FDA, Code of Federal Regulations Title 21 Part 820, Quality System Regulation. April, 2014.
6. Caldwell, Five Success Factors in Outsourcing, MDDI Guide to Outsourcing, March 2012