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Jan B.
Pietzsch
Department of Management Scienceand
Engineering,
Stanford University,
380 PanamaWay,
Stanford, CA94305-4026;
Wing Tech Inc.,
9916 Newhall Road,
Potomac, MD20854
Lauren A. Shluzas
Engineering,
and Department of Mechanical Engineering,
380 PanamaWay,
Stanford, CA94305-4026
M. Elisabeth Pat-Cornell
Engineering,
380 PanamaWay,
Paul G. Yock
Department of Bioengineering,
James H. Clark Center,
318 Campus Drive,
E-100,
John H. Linehan
Department of Bioengineering,
James H. Clark Center,
318 Campus Drive,
E-100,
Stanford, CA94305-5428;
Clinical and Translational Sciences Institute,
Northwestern University,
750 North LakeShoreDrive,
Chicago, IL 60611
Stage-Gate Process for the

Development of Medical Devices
The medical device development process has become increasingly complex in recent
years. The advent of new technology concepts, stricter regulatory requirements, and the
ever increasing importance of reimbursement decisions for successful device commercialization require careful planning and strategy-setting, coordinated decisions, and consistent, rigorous business processes. The design and implementation of such processes, often
captured in development models and accompanying standard operating procedures, have
become a key determinant of the success of device commercialization. While various
models may exist in the device industry, no comprehensive development model has been
published. This paper reviews existing model representations and presents a new comprehensive development model that captures all aspects of device development and commercialization from early-concept selection to postmarket surveillance. This model was
constructed based on best-practice analysis and in-depth interviews with more than 80
seasoned experts actively involved in the development, commercialization, and regulation
of medical devices. The stage-gate process includes the following five phases: (1) initiation - opportunity and risk analysis, (2) formulation - concept and feasibility, (3) design
and development - verification and validation, (4) final validation - product launch preparation, and (5) product launch and postlaunch assessment. The study results suggest that
stage-gate processes are the predominant development model used in the medical device
industry and that regulatory requirements such as the food and drug adminstration
(FDAs) Quality Systems Regulation play a substantive role in shaping activities and
decisions in the process. The results also underline the significant differences between
medical device innovation and drug discovery and development, and underscore current
challenges associated with the successful development of the increasing number of combination products.
!DOI: 10.1115/1.3148836"
1 I ntroduction
1
Medical devices contribute significantly to the continuous improvement of healthcare. With product lifecycles that are sometimes as short as 18 months, patients benefit from a continuous
stream of innovation that hinges heavily on successful needs assessment and the experience and skills of engineers and other
professionals involved in the innovation process. Yet, bringing a
new product successfully from the bench to the bedside is highly
complex and depends heavily on the implementation of rigorous
processes. These processes need to allow developers to optimally
1
In the context of this study, medical devices are defined as technologies used in
the diagnosis, cure, mitigation, treatment, or prevention of diseases or conditions that
do not achieve their primary treatment effect by pharmacological, immunological, or
metabolic means.
Manuscript received May 12, 2008; final manuscript received May 3, 2009; published online June 17, 2009. Review conducted by Paul A. Iaizzo.
Journal of Medical Devices
phase development, testing, and other activities, and to successfully execute on the manifold requirements of third parties, including regulators and payers. These additional requirements set
medical device development apart from the development of other
products.
The objective of the empirical study presented here is to give a
detailed overview and model representation of the medical device
development process and its various activities and decisions. The
motivation for this work is twofold. First, a thorough understanding of the multiple streams of activities and responsibilities in
device development can help engineers and other professionals to
execute the bench-to-bedside process of product development
most effectively. By understanding the intricacies and challenges
of development and commercialization, the development team can
better anticipate external requirements and their implications for
decision-making. This can contribute significantly to successful
product innovation, especially in light of the many startup companies that provide innovation in the medical device industry. Second, the ongoing efforts by regulators and policymakers to design
Copyright 2009 by ASME
JUNE 2009, Vol. 3 / 021004-1
Downloaded 17 Jun 2009 to 171.67.34.86. Redistribution subject to ASME license or copyright; see http://www.asme.org/terms/Terms_Use.cfm
Fig. 1 The product defi nition process based on Ref. 12
the least burdensome approaches to medical device regulation can

benefit from a thorough understanding of the invention and decision processes in medical device development.
The article is structured as follows. Section 2 reviews existing
development process representations. The methodology employed
for the interview and model building process is then introduced.
Section 4 presents the development model and detailed information about the various activities and decisions involved in the
process. Finally, the findings of the empirical study are discussed
and put in perspective.
2 Background
2.1 Product I nnovation and Development Process M odels.
Product innovation and the successful management of new product development has been the focus of both academic research and
managerial concern for more than 2 decades !1,2". At the heart of
these efforts is the development of an understanding of the factors
responsible for new product success, and the desire to drive new
products from idea to market faster and with fewer mistakes. This
also involves research on the optimal alignment of the New Product Development #NPD$ effort with the strategic objectives and
competencies of the firm !3", and more recently, questions of optimal product portfolios for innovating companies !4".
One of the most notable contributions of the last 2 decades has
been the development and implementation of stage-gate processes
for product development !5". These models are both conceptual
and operational tools to move a new product from idea to launch,
and recognize that product innovation is a process that can be
managed !5". A stage-gate system divides the innovation process
into a predetermined set of stages, separated by gates characterized by a set of criteria to be met before the product can advance
in the process. Each stage, in turn, is composed of a number of
prescribed activities that are in many cases related and that can
occur in parallel. Typical stages in a new product development
process involve preliminary assessment, detailed investigation,
actual development, testing and validation, and full production
and market launch #compare Ref. !5"$. The rigor of a stage-gate
process facilitates formal descriptions of various activities and
decisions. These descriptions are often summarized in standard
operating procedures and can be useful to define best-practice
approaches to development.
While applications of formal development processes and similar models have been described for a number of industries, including the automotive industry, no comprehensive process model for
new product development has been published for the medical device industry. Rochford and Rudelius !6" outlined a number of
stages and successes for the development of medical products, but
do not provide a comprehensive process description or summary
of activities and decisions. Kaplan et al. !7" described several of
the key activities of medical device development from prototype
to regulatory approval, but do not provide a model of the device
development process.
2.2 Existing Process Representations Associated With
M edical Device Development. A number of graphical representations have been published that delineate various aspects of the
medical device development process. They range from represen021004-2 / Vol. 3, JUNE 2009
tations of the product definition and quality function deployment

#QFD$processes to models of design control, and representations
of regulatory and reimbursement routes. Several of these models
are briefly presented Secs. 2.2.12.2.5 as an overview of the available literature and provide some perspective on the subsequent
model presented here. Additional background on medical device
development can be found in pertinent textbooks, including Fries
!8", King and Fries !9", Whitmore !10", and Kucklick !11".
2.2.1 Design Input and Product Definition Process Representation. Fries !12" graphically summarized what he calls the
product definition process, including customer needs, company
needs, company competency, and vendor/alliance competency.
The process representation shows the progression from specifications to available technologies and subsequent opportunities to
define applications, platforms, and enhancements based on the
developed technology concept #Fig. 1$.
2.2.2 QFD Matrices. In the context of design development
and refinement, QFD gained attention in the 1990s in some segments of the medical device industry. It is an overall methodology
that begins with the design process and attempts to map the
customer-defined expectation and definition of quality into the
processes and parameters that will fulfill them. QFD is closely
related to house of quality methods. A full understanding of the
various customer needs, constraints, and technical possibilities,
helps a manufacturer in planning processes and products that are
efficient and have high customer appeal.
QFD often takes the form of a comprehensive matrix that includes, among others, a customer information portion # voice of
the customer $ and a technical information portion. According to
Fries !12", a common result of QFD introduction is that building
the matrix becomes the main objective of the process, with positive results such as a more comprehensive understanding of patient needs. This, in turn, directly supports the development
process.
The detailed construction of QFD matrices, including assessment of quantitative data and relationships, is not discussed here.
Note, however, that QFD matrices and their representations can be
understood as partial development models.
Fig. 2 Application of design controls to waterfall design process 13
Transactions of the ASME
Fig. 3 Overview of a design change life cycle based on Ref. 14
2.2.3 Design Control Process Representations. The design

process is often graphically depicted in terms of relatively simple
waterfall diagrams. These diagrams link user needs through design input, design process, and design output to the completed
medical devices. Figure 2 shows a waterfall diagram that also
includes the iterative design control activities of Review, Verification, and Validation. While this model provides an understanding
of the interaction among various development stages, it lacks
some details, such as process requirements, health-economics, and
reimbursement planning, which are critical to the successful commercialization of a new medical technology.
Figure 3, based on Ref. !14", is a linear representation of the
device development phase, with focus on the design change lifecycle. It shows the four milestones Start to Plan, Start to Design, End Design, and Commence Building, with individual
tasks and activities between these milestones, and a description of
various design control outputs throughout the phases.
Stark !15" presented a schematic overview of clinical research
activities in the product development cycle #see Fig. 4$. The representation lists five product development phases #Concept
PrototypePrepilotPilotProduction$, and for each phase,
shows design control, product development, and clinical research
activities next to each other, including some of the major relationships among them.
Risk management, i.e., the anticipation and reduction of the
chances of failure and their consequences, is a critical element of
the design control activities that has received significant attention
from regulators and manufacturers in recent years. Figure 5
shows, in simplified form, the risk management process for medical devices according to ANSI/AAMI/ISO 14971:2000.
The FDA !16" has published a more comprehensive schematic
representation of the integration of risk assessment into the formal
design control activities #Fig. 6$. This description emphasizes
various methods, including fault tree analysis #FTA$ and failure
mode and effects analysis #FMEA$. It also puts verification and
validation activities2 in perspective. A comprehensive overview of
these methods can be found in Ref. !17".
2
Verification: Establishing conformance of design outputs to design input. Validation: Establishing conformance that final product meets user needs.
2.2.4 Development Cycle Representations. Several development cycle models exist. One of the most prominent devicelifecycle representations has been created at the FDA by Feigal
#Fig. 7$. The development aspect is covered in the first part of the
cyclic model #design through clinical sciences$. The model emphasizes the role of customer feedback and learning from one
generation of a device to the next, and shows the intertwined flow
of information. Comparable model representations can be found
in the literature, among them a representation by Califf et al. !19"
that emphasizes the clinical and quality aspects in the therapeutic
development cycle. The measures of quality and clinical outcomes
are particularly relevant for all health-economic and outcomesoriented considerations.
2.2.5 Regulatory and Reimbursement Representations. Several model representations of the device development and commercialization process exist to describe its regulatory and reimbursement aspects. These aspects are highly relevant for
development because they can have significant implications for
the design and testing of a new technology.
To represent the different regulatory pathways for medical devices, several flowcharts have been created. A comprehensive representation of the United States regulatory process presented by
Helmus !20" is shown in edited form #Fig. 8$. The figure outlines
the decision process that determines whether a device can be
brought to market via the 510#k$ premarket notification path, or
the alternative premarket approval #PMA$path. Note that exempt
devices #class I$ are not shown in this representation, and neither
are the product development protocol #PDP$ or humanitarian device exemption #HDE$ paths. Additional background and a detailed review of United States medical device regulation can be
found in Ref. !21". A detailed overview of the European device
regulation is given in Ref. !22".
3 M ethodology
The purpose of the present study was to construct a comprehensive representation of the medical device development process by
conducting a field study #between October 2006 and September
2007$ based on in-depth interviews of experts actively involved
with the development, regulation, and use of medical devices.
JUNE 2009, Vol. 3 / 021004-3
Fig. 4 Schematic overview of clinical research in the product development cycle based on Ref.
15
Among the interviewees were senior professional staff at the

FDA, and executives and other experts in medical device companies. Within the cohort of interviewees, all major groups involved
with product development, starting with engineering and strategic
planning to marketing and sales, clinical, and manufacturing, were
included. The companies ranged in size from startups to earlystage to major medical manufacturers such as Medtronic Inc., Biomet, Boston Scientific, and Edwards Lifesciences. The cases
studied ranged from imaging and surgical devices, to implantable
electrophysiological and mechanical devices, to drug delivery
technologies and in vitro diagnostic multivariate index assays
#IVDMIA$.
For this empirical study, the data collected initially were used to
generate hypotheses about the device development process. The
hypotheses were presented to subsequent interviewees and iteratively revised and improved. In addition to primary knowledge
generation through interviews, information available from the literature and other sources was used to build a body of knowledge.
This research approach, known as grounded-theory building, or
inductive theorizing, was chosen as a well established research
method to describe and understand complex phenomena #processes$from an empirical assessment of the diverse characteristics
of the investigated phenomenon !23".
Fig. 5 Schematic representation of the risk management process according to ANSI/AAMI/ISO 14971:2000
021004-4 / Vol. 3, JUNE 2009
The selected 86 interviewees comprised of individuals involved

at various stages of the development process, from research and
invention to early-concept definition, actual development, regulatory approval, and postmarket feedback. In order to ensure the
highest possible validity and generalizability of the results, interviewees were chosen from various backgrounds, technology areas, companies, and regions. In addition, we interviewed senior
FDA leaders, professional staff, and specialized consultants #regulatory affairs, reimbursement, clinical trials planning$of the medical device industry.
The protocol for the model construction process entailed several procedural steps as follows:
Review of standard operating procedures (SOPs) of four

device companies #large, midsize, and startup companies included$
Identification of different functional groups involved in device development process. To ensure identification and interview inclusion of the right constituencies involved in medical device development, a list outlining functional positions
and various job responsibilities was created.
In the first round of interviews, a representative sample of
the outlined functional groups was interviewed #ten interviews total, with R& D receiving particular attention$. All
interviewees were asked to share their perspective on the
development process, and to outline their individual activities and decisions in the development process # bench-tobedside $.
Based on the first interviews and reviewed SOPs, an initial
draft development model was constructed. This model outlined the different phases in the development process, and
the activities performed in each function during these
phases, including the decisions taken at various project
stages.
In a second round of interviews #50 interviews$, the initial
process representation was presented to interviewees, and
feedback was obtained. Based on this feedback, some additions and changes were made and continuously integrated.
Fig. 6 Integration of risk assessment with design control activities 16
In addition, the various activities and decisions identified in

the model were discussed in greater detail with each interviewee to ensure accurate and comprehensive description of
these activities and decisions as part of the model presented
here. A distinct decline of proposals for change in the model
over the course of the second round of interviews showed
convergence, and led us to conclude that the model presented in this paper was accepted by interviewees as an
accurate representation of the development process.
A third round of interviews involved the remaining 26 interviewees and focused on various specific aspects of the medical commercialization process based on the constructed
model. As part of the interview process, interviewees were
asked about the specific accuracy of our model. No additional changes or adjustments were suggested by the
interviewees.
4 Results
4.1 Constr ucted Development M odel. As outlined in Sec. 3
of this paper, construction of the device development model relied
significantly on insights acquired during the sequence of in-depth
interviews. The model is presented in linear-form as a stage-gated

process, according to the feedback and information obtained in the
field study. In reality, many of the defined processes within the
model are likely to be iterative. The linearity of the model is thus
a simplified representation of the actual process. To illustrate this
point, a number of typical iterative loops are presented after introduction of the linear model.
4.1.1 Linear Model of Device Development. The linear model
is shown in Fig. 9. Throughout the five phases of development,
activities are shown in conjunction with the various functional
groups responsible for them.
The linear medical device development model identifies five
major phases, separated by four decision gates. Predevelopment
activities occur prior to Gate I, development activities occur between Gates I and III, and product launch and postmarket assessment occur after Gate IV. In the model, the major functional
groups are identified in boxes on the left side of the chart. Major
decisions are shown #in parallelograms$ at the bottom of each
phase. Upper level activities for each functional area are highlighted in boxes within each phase. The horizontal progression
represents a generalized timeline. The major milestones/gates can
Fig. 7 Total product life cycle 18
JUNE 2009, Vol. 3 / 021004-5
Fig. 8 Regulatory pathways for medical devices representation based on Ref. 20. Legend: QS
Regulation: QSR; IDE: investigational device exemption; IRB: Institutional Review Board
occur at different times in the development process depending on

the type of device. The five major phases and decision gates include the following:
Phase 1/Gate 1:. initiation, opportunity, and risk analysis

Phase 2/Gate 2: formulation, concept, and feasibility
Phase 3/Gate 3: design and development, and verification
and validation
Phase 4/Gate 4: final validation, and product launch preparation
Phase 5: product launch and postlaunch assessment
It should be noted that although each development phase is

presented in a discrete manner, the iterative process of device
development does not always follow the linear idealized model,
but rather involves fuzzy boundaries between decision gates. Because of iterations in the process, some parts of a development
project may already be in a more advanced phase, while certain
activities of a previous phase need to be repeated at the same time.
The model describes a process that is most applicable to PMA and
510#k$ devices that require some form of clinical data, and to
devices that are largely mechanical in nature. The model can be
simplified for 510#k$devices that do not require any clinical data
regulatory clearance.
4.1.2 Description of Development Phases. In what follows,
each of the five development phases captured in the diagram is
described in greater detail based on the comprehensive interview
results. In addition, predevelopment activities that need to be
completed before the formal development process is initiated are
presented. For each phase, major responsibilities of selected functional groups are discussed. Deliverables for each phase and decisions faced at the four decision gates are collectively summarized in Table 1. The process can take anywhere from 15 months
to several years, depending on the type and complexity of the
technology, and the quality of process execution. Clinical testing
of some heart valves, for example, can take several years. Similarly, technologies that are used in a small population only, can be
delayed because of insufficient enrollment in trials.
021004-6 / Vol. 3, JUNE 2009
4.1.2.1 Predevelopment activities (phase 0). In order to create

a new medical device, inventors and device companies must focus
on the right clinical need. To that effect, a wide range of clinical
needs are first identified through direct observation, by speaking
with physicians, patients, and other health care providers, or
through personal experiences, and by a review of the relevant
clinical literature. Through a needs-finding funneling process #Fig.
10$, inventors take a first pass at narrowing a large list of clinical
needs based on the estimated market size and clinical impact associated with each. To further narrow the list down, inventors
usually examine prior art related to each need to determine if there
are barriers to further development from an intellectual property
perspective. This requires the very important step of defining preliminary product concepts. A preliminary market analysis is subsequently performed to ensure that there is a sufficient market
opportunity for each need. This analysis is expanded in Phase I.
Inventors must also determine if they are in a position to efficiently follow up in order to seize an existing market opportunity.
Once the list of clinical needs has been sufficiently narrowed,
each remaining need tends to get further validated in terms of
regulatory considerations, reimbursement strategies, intellectual
property, and business development objectives. In terms of company development, the process is to further check that the product
fits the company strategy and that the company has the capability
of successfully commercializing the product.
4.1.2.2 Phase I: Initiation - opportunity, and risk analysis.
The predevelopment activities within Phase I mark the beginning
of the medical device development process, as defined here. In
some instances, this phase is also referred to as technology
phase. It is characterized by the early evaluation of projects
aimed at addressing clinical needs as described in Phase 0. Verification of the previously identified clinical need might involve
talking to physicians, patients, and hands-on technology users,
such as nurses, operating room and lab technicians, and observing
them in the clinical setting. This phase also involves a review of
the existing medical devices and procedures that are being used to
Fig. 9 Linear medical device development model
treat the condition. Next, a preliminary market analysis, financial

review, and competitive product assessment are often performed.
A review of the existing IP landscape within a specific market or
pathology area is also conducted, as well as an early-stage techJournal of Medical Devices
nology risk assessment. The IP review includes evaluation of the

technology concepts that have been identified in Phase 0 and I.
Potential regulatory paths and their associated risks are studied
and initial reimbursement strategies assessed.
JUNE 2009, Vol. 3 / 021004-7
Table 1
Deliverables and decisions at decision gates for Phases IIV of development model
Understanding the market for a proposed medical device and

the likely financial return on the investment are critical components of the predevelopment phase. Note that each of the activities
listed in the development model can include several subactivities
that are not explicitly shown on the diagram. Also, many dependencies can exist between the listed activities. Financial Review, for example, depends heavily on the results of other activities such as market analysis, competitive assessment, technical
feasibility, etc.
Market analysis/competitive assessment

Market analysis involves needs assessment and validation, demographics analysis, a SWOT #strengths, weaknesses, opportunities, threats$ analysis to examine a products strengths, weaknesses, opportunities, and threats; market research aimed at
identifying the market size and growth potential; and a competitive outlook analysis. Product positioning and launch strategy are
also key elements to medical device predevelopment activities.
Analysts examine the current product mix and determine how the
Fig. 10 Needs-fi nding funneling process and relationship to product development model
021004-8 / Vol. 3, JUNE 2009
new device should be ideally priced and positioned to make the

greatest market impact, without cannibalizing existing sales !12".
Marketing and promotional launch activities are also examined at
that time.
Financial review
Once the market for a proposed medical device has been identified, it is necessary to perform a thorough financial review. Financial analysis entails calculating sales projections and projected
gross margins for a particular device or a proposed market !12". In
addition, a financial analysis often includes a proposed royalty
breakout for physicians who contributed either to the primary device concept or to intellectual property toward the development of
the proposed device. A financial analysis may also include an
assessment of what would happen if the device is not introduced
to the market at the present time, or if it is introduced at a later
time #i.e., the pros and cons to having a first-mover advantage$.
Projected inventory analyses are often performed in order to assess the number of units that would need to be built in order to
satisfy market demands.
Legal/IP analysis
The initial review of the IP landscape during the predevelopment phase involves conducting a preliminary search of patents
within and outside of the United States, including both applications and issued patents. Depending on the existing IP landscape,
a risk assessment is made to determine whether or not pursuing
device development would be a viable investment !12". The preliminary IP review can also be used to establish design boundaries. In order to avoid IP violations, licensing agreements may be
considered at this time if existing IP was generated from independent inventors #as opposed to major business competitors$.
Regulatory and clinical path
The early-stage regulatory review involves identifying the preferred domestic regulatory path, based on the type of proposed
device and its market entry point #i.e., as a breakthrough product,
line extension, addition to product family, etc.$. An international
regulatory assessment could be performed to determine the information needed to obtain a conformitee europeenne #CE$mark #for
marketing of a device in the European Union$ or other foreign
regulatory approvals for the proposed product. A regulatory risk
assessment and preliminary clinical plan assesses whether the approval process will require clinical trials !12". The early regulatory review is particularly important for a device manufacturer,
because investment in a project with high regulatory risks could
result in a net loss for the company if the device is not approved
for use or if it requires unanticipated additional clinical studies
prior to launch.
Reimbursement strategy
In order to commercialize a medical device, companies often
develop an early-stage reimbursement strategy. It is critical for
companies to determine what will be required to secure a payment
strategy, and how long it might take to implement such a strategy:
Understanding potential reimbursement rates is also imperative
for effectively pricing a new product. Particularly in medical devices, where the lifecycle from concept to launch is relatively
short, entrepreneurs need to develop plans and processes to obtain
reimbursement coverage prior to market entry. This is important
to facilitate market acceptance and help generate increased demand, !24".
Phase I: Deliverables and decision gate
The major deliverables of phase I and the key decisions to be
made at the decision gate are summarized in Table 1. A key deliverable of Phase I is a business plan that is built on information
collected during this phase. The elements of the business plan
include market assessment, unmet needs, product description, financial plan #P& L$, R& D plan including resource plans, regulatory and clinical plan, marketing plan, manufacturing plan, distriJournal of Medical Devices
bution plan, reimbursement plan, sales and distribution plan,

supply chain strategy and plan, and a risk analysis for the various
factors beyond pure design risk. The business plan is usually written before major investments are made. The information contained
in the plan is critical to receiving project approval from management and resources for the project, or for a small company, capital
from investors.
4.1.2.3 Phase II: Formulation - concept and feasibility. If the
project is accepted by upper management, development proceeds
to Phase II. Concept formulation and feasibility assessment occur
during this stage. A cross-functional project team is selected #often
referred to as project core team $, and a general project plan and
timeline is created !12". The team usually includes lead members
from R& D, quality assurance, manufacturing, marketing/sales,
regulatory, clinical, and legal roles. Creation of a design plan is a
formal requirement #per 21 CFR 820.30$ and signals the beginning of formal design controls. The R& D core team member often
leads device development during Phase II and assumes the role of
project manager. There are exceptions, in which case a separate
project manager will oversee timelines and general project plans.
The team leader is responsible for initiating and managing the
design history file #DHF$, or a record indicating that the device
was developed in accordance with the approved design plan
!25,26". The design plan is governed by FDAs Quality Systems
Regulation and needs to be defined by senior management.
Lack of adequate records is a frequent cause of audit failure and
can jeopardize the project timeline and ability to support regulatory filings. During the early development phase, the teams marketing associate and R& D engineer often meet with potential users #physicians, nurses, technicians, patients, among others$ to
obtain customer input. Users state their needs, requirements, and
early design inputs #per 21 CFR Part 820.30$. User input, at this
stage, may range from a napkin sketch to a complete patent proposal that can be commercialized. It also is common for new
device ideas to be generated from considering existing product
complaints, which are either communicated directly from physicians or reviewed from the FDAs MAUDE complaint database.
User input enables device designers to gain a better understanding
of the competitive landscape in a particular medical specialty area,
and may motivate or dissuade a development team from pursuing
a proposed device.
Voice of customer/customer design input
Both during this early stage of development and throughout the
development cycle, marketing is the functional area responsible
for listening to the voice of the customer #VOC$and ensuring that
user needs are met. Design inputs might include items such as the
intended use of the device, testing requirements, biocompatibility
requirements, functional requirements, and physical requirements
#i.e., size, material, packaging, sterilization, environmental compatibility, and appearance$ !26". Marketing also participates in
early-stage prototype evaluations by customer physicians, in conjunction with the R& D group.
Concepts/prototype analysis
During Phase II, R& D is responsible for generating more elaborate concepts, based on the design inputs received from a teams
marketing associate and/or potential device users. Brainstorming
sessions are often held during this stage of development with
members of R& D, marketing, and physician consultants. Prototype development and design analysis is often a highly iterative
process, whereby device designs are frequently changed and refined before the final design is established. A three-dimensional
solid model of a proposed device is often developed in order to
conduct computational analyses and construct physical prototypes. Computational analyses, such as finite element analysis
#FEA$or computational fluid dynamics #CFD$, may be conducted
to understand the theoretical behavior of a proposed device.
Physical prototypes, such as mock-ups and stereolithography prototypes #SLAs$, are often evaluated in bench, cadaver, and early
JUNE 2009, Vol. 3 / 021004-9
animal studies, to test the physical performance of a device. Continuous interaction among engineers and future device users is
critical during prototype development, in order to ensure that the
new device will satisfy end-user requirements. Likewise, as a device becomes more refined through multiple prototype iterations
and feasibility studies, the IP landscape is continually reviewed,
and potential legal and liability risks are assessed. Throughout
Phase II, R& D will often hold design reviews #per 21 CFR
820.30$ with all cross-functional team members in order to systematically assess a devices design progress. It should be noted
that many companies begin prototyping efforts as early as Phase I
to inform their financial planning and support definition of their
product development strategy.
Design risk analysis/risk management
Risk management is a critical component of the analysis, prototype, and design development phases. The FDA expects companies to have a complete risk management plan and system in
place, which consists of the two aspects of risk analysis #identification and quantification of risks$ and risk management #mitigation of the identified risks$. Several years ago, the industry supported the creation of ISO 14971, which covers risk management
for medical devices and outlines specific methods to identify and
address risk. This standard is now cited in many other standards
and has been recognized and adopted in many countries.
A number of tools exist that are commonly employed to conduct risk analysis and management during Phase II: Design Failure Modes, Effects, and Criticality Analysis #dFMECA or
dFMEA$is used to recognize and evaluate the potential failure of
a product or process and its effects !26". dFMEA is also used to
identify and prioritize actions that could mitigate the chance of a
failure. FTA is another common risk assessment tool. FTA uses
logic block diagrams that display the state of a system #top event$
in terms of the states of its components #basic events$. It can be
used to capture failures resulting from both human errors and
hardware failures. Risks are mitigated to an acceptable level
generally as safe or safer than existing devices used for the same
purposes. Actual mitigation of risks needs to be verified as part of
the design process. In the remainder of this paper, the term risk
analysis is in several instances used as a short form for risk
analysis and risk management. It explicitly includes risk mitigation efforts.
Design for manufacturing
Initial design for manufacturing #dFM$ efforts begins in Phase
II, in parallel with device concept and prototype development
!12". dFM involves developing an initial plan for how fixtures will
be made, how tooling will be developed, what machines should be
used for the devices manufacturing process, and whether or not
molds need to be created in order to build prototypes for verification and validation testing. For devices that build on existing devices on the market, a significant portion of manufacturing work
can be performed at this early development stage. However, for
breakthrough products, manufacturing largely supports R& D prototype efforts during Phase II, while contributing suggestions as to
how proposed devices can be manufactured for high-volume production.
Regulatory and reimbursement strategies
The initial regulatory and reimbursement strategies that were
initiated in Phase I are further developed during the concept and
feasibility stages of development. Different options are examined
regarding which regulatory path to pursue #for the United States
market, for example, 510#k$ versus PMA; for Europe, different
routes to CE marking; etc.$and whether or not clinical studies will
be required. The reimbursement team assesses whether or not existing reimbursement codes #for the United States market, e.g.,
CPT3 and DRG,4 for international markets, the codes used in the
3
CPT: Current Procedural Terminology
021004-10 / Vol. 3, JUNE 2009
respective countries$ can be applied to a proposed device, and if

so, the amount that insurers and users might be willing to pay for
the proposed technology !27". Reimbursement information feeds
directly into early-stage device development since it establishes a
price point that design and manufacturing efforts should target in
order to build devices capable of generating sufficient profit margins.
Phase II: Deliverables and decision gate
The major deliverables of Phase II and key decisions to be
made at the decision gate are summarized in Table 1.
4.1.2.4 Phase III: Design and Development - Verification &
Validation. After a device concept has been formulated and several prototyping rounds have occurred to assess feasibility, the
development proceeds into Phase III. During that phase, a verification and validation test matrix is created by cross-functional
team members. The matrix is intended to outline the verification
and validation #V& V$tests that occur both before and after design
freeze #Phases III and IV$, as well as to provide a foundation for
formal validation testing in Phase IV. V& V testing is conducted
primarily by research and development, test engineering, and
quality engineering. Marketing often participates in validation
testing, such as physician prototype evaluations. Verification and
validation studies including their methods of documentation are
subject to design controls. Without proper documentation, the
studies may not be usable from a regulatory standpoint since all
V& V studies must be reproducible.
Verification testing
Design verification characterizes a device through feasibility
studies and verification testing, and ensures that device development complies with the quality system #QS$ regulation, 21 Code
of Federal Regulation Part 820. Design verification also involves
testing and inspecting a device to ensure that design outputs satisfy design inputs. Testing examples include analytical, preliminary performance, biocompatibility, and durability/longevity tests.
An example of design inspection includes performing tolerance
stack-ups on prints and drawings. Verification also involves a
wide range of feasibility studies, including bioburden, exposure/
environmental, sterilization, cleaning, and packaging/ship testing
!26".
Validation testing
Customer prototype evaluations continue in Phase III to assess
final prototypes, prior to design freeze. These types of validation
activities ensure that the new device successfully meets user needs
and requirements !26". Design validation in Phase III involves
simulated use tests, which may require the use of anatomy models
and/or cadavers. Design validation can also require studies to investigate user interfaces and human factors. Validation could also
include tests such as mechanical testing, clinical evaluations by
physician user groups, biocompatibility studies, mating part functional tests, exposure/environmental testing, or packaging/
shipment testing and sterility. Human factors are an important
consideration in validation testing, and have recently received increasing scrutiny by regulatory agencies.
Risk management and process validation
Risk management in Phase III involves collaboration among all
members of the cross-functional team, with particular emphasis
on the quality, manufacturing, and R& D functional areas. Design
control deliverables, such as the dFMECA are updated during this
phase. The development team initiates the process FMECA
#pFMEA or pFMECA$to ensure the success of the manufacturing
process and the production of safe and effective medical devices
!26". A process validation plan is also created in Phase III to
ensure that a manufacturing facility is in compliance with GMPs
#Good Manufacturing Practices; part of the FDAs Quality Sys4
DRG: Diagnosis Related Groups
tems Regulation$. A process plan involves a protocol for an installation qualification #IQ$, operational qualification #OQ$, performance qualification #PQ$, and product performance qualification
#PPQ$ !28". After a design is frozen at the end of Phase III, a
process validation plan is often executed by the teams manufacturing engineer and quality engineer in Phase IV. Process excellence tools such as Lean Six Sigma are commonly employed in
this phase and the subsequent phase of the development process.
Regulatory and clinical
During Phase III, several additional activities are conducted by
members of the regulatory and clinical departments. Regulatory
activities include submitting design and test data to the FDA for
review and regulatory approval. FDA submission is a major milestone in the device development process. Preparing for a submission requires a strong collaboration among several crossfunctional areas, such as clinical, R& D, quality, and regulatory.
The regulatory group of a product development team generally
includes a Regulatory Affairs associate who handles submissions
and market clearance, and a Regulatory Compliance associate
who administers the quality system. A teams regulatory group
oversees the completion of requirements needed for international
product use, such as the European CE mark mentioned earlier. If a
device requires clinical trials for regulatory submission, the teams
regulatory group submits an investigational device exemption
#IDE$ to allow the device to be used in a clinical study !25".
Regulatory associates will also oversee the clinical trials, analyze
results, and submit data required for regulatory submission. Clinical trials are of substantial importance for the successful commercialization of medical devices, and thus need to be carefully
planned and conducted. A detailed discussion of the various considerations for clinical trial planning is beyond the scope of this
paper. Additional background and information on this topic can be
found in pertinent textbooks !2931".
Patent review and reimbursement update
The patent review process is continued in Phase III #sometimes
also earlier, in Phase II$to ensure that initially filed IP is sufficient
to protect the developed technology, and to perform a second
check on possible conflicts that could limit the companys freedom to operate !32".
The devices reimbursement strategy is further established in
Phase III, as reimbursement codes and part numbers are assigned
to the new device.
Phase III: Deliverables and decision gate
The major deliverables of phase III and key decisions to be
4.1.2.5 Phase IV: Final validation - product launch
preparation. Phase IV of the medical device development is characterized by the creation of formal design prints, final product
verification and validation, sales launch preparation, and regulatory approval.
Final design drawings and specifications
Once a design is frozen, formal manufacturing prints are generated for the new device, consisting of both component and
assembly-level drawings. Final prints must conform to geometric
dimensioning and tolerancing #GD& T$ standards to ensure that
design requirements are effectively communicated to suppliers
and manufacturers. The same holds for final specifications of electronic components. Tolerance stack-ups are also conducted on the
final design to ensure that there are no mating part interferences
within a device, or between a device and another instrument with
which the device interacts !12". Material specifications, packaging
drawings, and marking and labeling specifications are also finalized during Phase IV.
Design and process validation
Closure of recommended risk mitigating action items per the
companys risk management system #compare earlier comment
about ISO 14971$ occurs during the final verification and validation phase of device development. These accompanying design
control deliverables are living documents, which remain active
throughout the life of the device. A process validation/
qualification plan, which includes an IQ, OQ, PQ, and PPQ, is
executed by a quality engineer and a manufacturing engineer in
Phase IV. The IQ documents that a correct manufacturing instrument was received and installed properly, an OQ tests that an
instrument meets specifications in the user environment, and a PQ
tests that the system performs the selected application correctly. A
PPQ demonstrates that the process has not adversely affected the
finished product and that the product meets its predetermined
specifications and quality attributes !33". In Phase IV, manufacturing efforts are often scaled-up in preparation for high-volume
development, although not all production efforts require highvolume scale-up. Statistical process control #SPC$ standards are
established !26" during this phase of development, and a number
of specific indices are commonly used in this context. The socalled Cp is an indicator of process capability !12". Cpk, the
process capability index, involves the adjustment of Cp for the
effect of noncentered distributions. That is, Cpk measures how
close a process is running to its specification limits, relative to the
natural variability of the process !34".
Sales launch preparation
Several sales and marketing activities must take place prior to
the launch of a new medical device. A critical decision that must
be made at the outset of this process is the choice of the appropriate distribution channels, and whether internal or external sales
representatives will be used. A teams marketing associate must
prepare and equip sales representatives with items such as a surgical technique guide that defines how the device is used, videos
illustrating product use, and sample product kits for physicians.
The device is often advertised in medical journals and then showcased at a large meeting or medical conference for physician customers. Sales rep training sites are established, and a training protocol is created for both sales reps and physicians. Specific
hospitals, often referred to as limited market release #LMR$sites,
are identified for initial product release. Product branding occurs
in Phase IV, as marketing works with the legal department to
conduct trademark searches in an effort to determine an appropriate product name. Also, an artist or marketing communications
firm is often hired to create a new logo for the device. Finally,
marketing must communicate with manufacturing and operations
to ensure that product inventory/launch quantities will be available to fulfill projected sales forecasts.
FDA approval, quality systems, and reimbursement
A key requirement that must be fulfilled before a medical device can be launched in the United States market is regulatory
approval/clearance by the FDA. This requirement includes the development and implementation of a working quality system. Also,
a companys reimbursement strategy for the new device must be
finalized in Phase IV. Clinical validation continues before and
after FDA approval has been granted in order to continue monitoring device performance and possibly expand a devices indications for use.
For new medical devices, establishing a quality system is a
large critical task. If the product is a line extension to an existing
device or product family, then a quality system may already be in
place and working well. The quality system starts with defining,
documenting and formally approving and releasing %90% of the
business document/systems, both product specific #product spec$
and administrative #purchasing controls$. This is a resource intensive, time consuming task on a scale similar to the development
process. It is normally done in parallel with the product development, and cannot be done retrospectively.
JUNE 2009, Vol. 3 / 021004-11
Phase IV: Deliverables and decision gate

The major deliverables of Phase IV and key decisions to be
4.1.2.6 Phase V: Product launch and post-launch assessment.
Final product launch and postmarket surveillance occur in Phase
V of the medical device development cycle. Centers of excellence are hospitals, labs, or physicians office used for initial
product release. These include hospitals and medical centers
staffed with physicians who have received prelaunch training in
the use of the new device. These sites can be identical with the
previously mentioned LMR sites, but do not have to be. Once a
device has proven successful in a limited number of medical facilities, it will be marketed and distributed for widespread clinical
use. A peer-to-peer physician education model is often used to
seed marketing and promote rapid product adoption. That is, physicians who helped to develop a product and who participated in
validation testing are often involved with regional and local training sessions #i.e., cadaver, bioskills, or didactic$. Clinical trials are
frequently performed by select physicians following product
launch. These trials aid in gaining reimbursement support and
additional marketing literature, as well as expanding further indications for use, which requires FDA approval.
Post-launch R& D
Following product launch, R& D efforts are transferred to engineers responsible for managing design changes, often referred to
as process engineering groups. This functional area is responsible
for the continual improvements and changes made to either the
product itself or the processes used to create the product throughout the life of the device. When a product complaint is received
from the field, one of several courses of action may be taken: for
instance, a label change !35" occurs when an aspect of the device
has failed that was not properly indicated on the instructions for
use #IFU$; a customer/feasibility change is made to satisfy the
requests of a specific physician customer; and a total product redesign may occur when there is a major flaw in the design and/or
when the product has been recalled !36" from the market by the
FDA.5 Design control deliverables are required throughout the life
of a medical device. The Device master record is released as part
of the design transfer process, and in it, further design changes are
managed. In addition, companies need to implement a postmarket
surveillance system that is compliant with the Quality Systems
Regulation. Surveillance and reporting of product performance in
the field has recently received increasing attention by the FDA,
partly as a result of highly publicized product recalls.
4.1.2.7 Iterations in the development process. A typical pattern of medical device innovation is its iterative nature. In many
cases, technologies are developed in several generations, with the
next generation of a device incorporating new technological insights and experiences gained during field use of the previous
generation of a device. In many technologies, lifecycles are thus
very short. Similarly, the development process of a specific generation of a technology can be highly iterative, with various activities and decisions in the linear model revisited. Such iterative
loops include design improvements based on clinician feedback,
redesigns after failed verification or validation testing, or design
improvements based on unexpected results of bench and animal
testing #so-called preclinical testing loops$. Therefore, as pointed
out earlier, the linear stage-gate model should not be misunderstood as accurately describing what in reality can be a highly
iterative process.
Figure 11 shows a typical example of such iteration, in which
unsuccessful verification and validation testing leads to redesign
and retesting of the product. Note that a critical decision in the
5
Note that recalls do not necessarily need to result in a withdrawal and redesign of
a product. In many cases, recalls are handled with field corrections or notices to
users.
021004-12 / Vol. 3, JUNE 2009
Fig. 11 Design iteration based on failed verifi cation and

validation
design process is design freeze, after which no element of the

products design is allowed to be changed anymore. A late design
freeze may reduce the likelihood of a subsequent iteration, but
also can lead to a substantial delay in bringing the product to the
market. Finding the right balance between the two alternatives can
be a major challenge for the development team. A similar challenge is the appropriate determination of the value and benefit of
iterations. It is obvious that iterations of high-cost activities, such
as clinical trials, should be avoided whenever possible.
5 Discussion
Several activities within the device development process have
been represented as schematic models in the past, among them the
quality function deployment, risk management, and regulatory approval processes. Similarly, a number of overarching models of
the development and commercialization process have been published in the past, for example, the FDAs waterfall model or the
representation of the commercialization process of PMA devices.
None of these representations, however, document comprehensively the medical device development process.
The feedback and responses obtained from interviewees during
the model building process led to a relatively rapid convergence
toward the final linear stage-gate structure presented here. In conjunction with the diverse empirical sample, this suggests that the
constructed model applies to a broad range of medical technologies and innovation settings.
The stage-gate process is comprised of five phases from
initiation/opportunity and risk analysis to postlaunch and postlaunch surveillance. Some minor process differences exist for devices requiring clinical studies #the so-called IDE process for
PMA devices and 510#k$ devices that require clinical data$, and
for non-IDE devices #the technologies not subject to clinical
evaluations during development$. The model presented in this paper embodies the more complete process by including clinical
studies.
The apparent uniformity of the development process across devices and types of companies can be explained by the promulgation of the very detailed and comprehensive Quality Systems
Regulation #QSR-21 CFR 820$ by the FDA. The QSR prescribes
the elements of the design process, including definition of design
input, design output, specification development, testing, risk
analysis, process qualification, etc. A review of the document
shows that significant aspects of the development process are governed by, or at least subject to, regulatory requirements. Regulatory requirements substantively impact the manner in which medical devices are developed and brought to market and, by
impacting the time to FDA approval, largely determine when the
device can brought to the clinic. By standardizing the development process, the public is assured that critical elements of good
design practices are not omitted. But standardization does not always permit streamlining developmental processes where it would
make sense.
It should be appreciated that nonadherence to regulatory requirements #and thus, nonadherence to a systematic development
process as the one outlined in this study$ can lead to significant
delays or even the discontinuation of device development. As
such, knowledge about the regulatory requirements and a rigorous
quality system and documentation process are essential success
factors of any device company. In the public discussion, their
impact might sometimes be underestimated, as the focus of discussion is often limited to the regulatory pathways to approval and
the associated data requirements. Early, innovation-oriented technology assessment during development #see, for example, Ref.
!37"$that takes these requirements and the expected performance
of the technology into account, may present an opportunity for
both industry and regulators in further streamlining the innovation
process.
Despite the benefits associated with a rigorous process and
clearly defined procedures, innovation often occurs in a nonlinear,
less structured way, sometimes under unexpected circumstances.
In implementing development processes in organizations, it is
therefore necessary to strike a balance between sufficient process
rigor and enough room for flexibility and creativity. It can be
argued that evolutionary product development benefits from structure, while revolutionary product development is catalyzed by a
less rigorous process environment. Striking the appropriate balance presents a continued challenge for any organization inventing and developing technologies, and will often require adjustment of general process structures to the individual requirements
of an organization. Complexity in process management is added
when innovation is not a purely internal process within an organization, but requires outside collaborations, in-licensing and integration of new technologies, processes, or competences. This is
often the case in medical device development.
Drug-device differences and their implications
Several important differences exist between medical devices
and pharmaceuticals in general, and their development processes,
in particular, #compare, for example, Refs. !38,39"$. These differences need to be understood to appreciate the inherently different
development processes and regulatory requirements between devices and drugs. Drug-device differences are also important to
understand since they help elucidate the challenges associated
with the development of combination products, which increasingly blur the distinctions between medical devices and pharmaceuticals.
Discernable differences between classic devices and drugs
#not considering cells and biomaterials$ include the following:
Devices tend to be more heterogeneous #see below$ as a

group than drugs.
Devices usually have a localized treatment effect, as opposed to the often systemic application found in drugs.
Devices are engineering-based physical objects, while drugs
are chemistry-based compounds.
Devices tend to require significant user interaction, while
pharmaceuticals do not.
Devices are invented, often with the involvement of physician users; pharmaceuticals are discovered in laboratorybased research processes
The phrase device heterogeneity refers to the wide differences in mode of operation, and the wide variety of technologies
with attendant indication-specific design features #ranging from
tongue depressors and implantable joints to implantable defibrillators and artificial corneas$. Among other factors, heterogeneity
leads to a much wider variety in the way devices are tested #e.g.,
wide differences in the types of bench studies performed$ and
regulated. While all new drugs are subject to a single approval
process, medical devices can be approved through various regulatory pathways with differing requirements that influence the duration and complexity of the development process. A major reason
for the different risk-based regulatory pathways for devices is the

engineering-based nature of devices, which makes the risk profile
more easily understood and quantifiable. This is a substantive difference to drugs, which require comprehensive toxicology, pharmacokinetic and pharmacodynamic tests for their approval.
One of the results of the differences in the regulatory approval
processes for devices and drugs are the usually shorter lifecycles
for medical devices. Once the basic safety and effectiveness profile of a device has been evaluated, testing and approval of new
generations of the device can leverage already existing information about the device. Shorter lifecycles in devices are also evidence of the important role of user feedback in device innovation.
Integration of user feedback can significantly increase the usability and effectiveness of a device, and is a major impetus driving
product innovation for the benefit of patients.
The fundamental differences between the science-based drug
discovery process and the engineering-based, hands-on device invention and development process also lead to vastly different
capital requirements. These differences are evident in the structural differences between the medical device and pharmaceutical
industry. While the medical device industry is much more fragmented, with many small to midsize companies contributing to
innovation, the pharmaceutical industry is dominated by a small
number of large companies that have the financial resources to
support the much more costly pharmaceutical development process.
The differences between drugs and devices also result in different quality system requirements, which lead to substantial differences in the way testing and manufacturing processes are designed and managed. For example, shelf-life requirements as part
of the validation process play a much more significant role in
pharmaceuticals. Similarly, batch testing is a standard requirement
in drug manufacturing and is not required in medical devices.
Combination product development
Drug-device combinations such as the drug-eluting stents as
well as other combination products that involve combinations of
devices with biomaterials or cells begin to play an increasingly
important role in health care innovation. In light of the device
development model presented here and the discussed differences
between device and pharmaceuticals, some of the challenges and
opportunities of combination product development and their resulting implications are briefly discussed here.
On the regulatory side, FDA has responded to the increasing
number of combination products with the creation of its Office of
Combination Products #OCP$ in 2002. OCP has the coordinating
responsibility of assessing combination products throughout their
product lifecycles !40". The primary regulatory responsibilities,
however, remain with one of the product centers #Center for Drug
Evaluation and Research #CDER$, the Center for Biologics Evaluation and Research #CBER$, or the Center for Devices and Radiological Health #CDRH$$, based on the products primary mode of
action. This means that the principal regulatory pathways of the
respective centers areuntil nowstill guiding the review and
approval process !41". A combination product assigned to the Office of Device Evaluation #ODE$, for example, is subject to the
regulatory requirements outlined earlier.
The nature of certain activities outlined in the stage-gate development model are influenced by differences in preclinical #bench
and animal$ testing !42". For drug-coated devices, for example,
fatigue and corrosion testing of drug coatings requires new benchtop test methods employed to ensure that drug coatings do not
crack or flake-off during extended product use !43". Also, in
terms of testing for shelf-life and stability, combination products
present new challenges for preclinical testing. The testing of traditional bare medical devices often uses the effects of accelerated aging to simulate the effects of real-time aging. Yet, when
drug compounds become part of a product, the effects of drug
compound stability must be carefully examined, in terms of drug
elution, impurities and particulates !43,44".
JUNE 2009, Vol. 3 / 021004-13
Verification and validation activities, outlined in Phases III and

IV of the linear stage-gate model, also have to be adapted in
certain types of combination products. As mentioned earlier, the
current good manufacturing practices #cGMPs$ for drugs and devices are different, hence following different regulations and applicable standards. The cGMPs for finished pharmaceuticals or
drug products are codified in 21 CFR Parts 210 and 211. Devices
must be manufactured in accordance with the QS regulation, per
21 CFR Part 820. When marketed separately or when manufactured separately as constituent parts of a combination that will
later be combined, each part of a combination product remains
subject only to its governing cGMP regulations #21 CFR 3.2$.
However, if combination products are produced as a single entity
or are copackaged, both sets of cGMPs are applicable during and
after joining the constituent parts together. Therefore, companies
are challenged to ensure that combination products comply with
one or both manufacturing standards, as needed !45".
Unlike noncombination medical devices, which can undergo
process changes rather quickly, combination products require
manufacturers to carefully study a drugs output and stability
whenever a products manufacturing process is modified. In addition, manufacturers of combination products must perform more
product and process characterization earlier in the development
cycle than they would with traditional devices, !46". In terms of
product characterization, traditional medical devices are often
manufactured from well characterized raw materials; but combination products involve the use of novel drug excipients, which
must be fully characterized early in the development process.
Combination product development is largely influenced and
challenged by the differences in innovation cycles between pharmaceuticals and medical devices. Pharmaceutical innovation
cycles tend to occur every 1020 years !47", whereas devices can
become obsolete within a period of months. Therefore, in order to
produce new products on a more frequent basis, combination
product manufacturers may choose to innovate through developing new device delivery systems that are compatible with existing
drug therapies #e.g., new generations of a drug-eluting stent$.
However, robust material testing and a complete evaluation of
device/pharmaceutical interactions must occur for every device
iteration !46", again requiring adjustments in the linear stage-gate
development model.
The development of combination products is distinctive in that
it requires integrating the knowledge base of several disciplines
#i.e., biology, chemistry, and engineering$, each of which rely on
specific terminology and design methodologies. Consequently,
companies developing combination products must establish a
team structure that is different from that of either traditional pharmaceutical or medical device development !45". For example, in
addition to the functional areas presented in the linear stage-gate
model of device development, combination product development
requires an additional R& D analytical testing group. Merging
teams of individuals from pharmaceutical and device development, in general, will require increased cross-functional coordination !46".
Based on these differences and additional challenges, it should
be evident that the development process of combination products
is more complex than the classic medical device development
process. Some of the most notable adjustments that need to be
made if the linear stage-gate process model is used in combination
product development include the following: #1$ Drug-dosing and
coatings need to be established prior or during Phase I of the
development model; #2$ an additional R& D analytical testing
group needs to be added; #3$ new preclinical testing modalities
need to be considered for Phase II; #4$for specific products, both
the device and pharmaceutical quality systems need to govern
activities in Phases III and IV of the process; and #5$ supplier
quality is required as a separate group in combination product
development, distinct from the manufacturing and operations
groups in the traditional device development process.
021004-14 / Vol. 3, JUNE 2009
6 Conclusions
The linear stage-gate model gives a comprehensive description
of the various activities and decisions associated with the development of medical devices. A good understanding of this process
can benefit all stakeholders in the bench-to-bedside process of
device commercialization: investors, who need to allocate their
resources in the most efficient way, and who need to understand
the funding requirements of different types of development
projects; engineers and researchers who aim at improving the design and benefit of a technology; and regulators who need to ensure the safety and effectiveness of new products in the most
efficient way.
The process mapping presents several opportunities for the development of quantitative models to support decision-making at
various levels. First, information can be used to create early-stage
technology assessment and risk management models to inform
engineering and funding decisions. These models can subsequently be integrated into more comprehensive lifecycle risk management models that allow for continuous updating of failure risk
and the expected performance of new technologies, information
that can be very useful to both industry and regulators.
As discussed in this paper, the medical device development
process differs substantially from the development process for
pharmaceutical products. An appreciation of these differences is
essential to the appropriate design of future development models
and regulatory requirements for various types of combination
products that cross the line between devices, pharmaceuticals, and
biomaterials.
Acknowledgment
This paper was written based on the research performed by the
authors as part of a study Medical Device Development Models,
funded by the Institute of Health Technology Studies #InHealth$.
The authors gratefully acknowledge the financial support by InHealth.
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Jan B.

Stage-Gate Process for the

Journal of Medical Devices

Copyright 2009 by ASME

JUNE 2009, Vol. 3 / 021004-1

Fig. 1 The product defi nition process based on Ref. 12

the least burdensome approaches to medical device regulation can

tations of the product definition and quality function deployment

Fig. 2 Application of design controls to waterfall design process 13

Transactions of the ASME

Fig. 3 Overview of a design change life cycle based on Ref. 14

2.2.3 Design Control Process Representations. The design

Journal of Medical Devices

Among the interviewees were senior professional staff at the

021004-4 / Vol. 3, JUNE 2009

The selected 86 interviewees comprised of individuals involved

Review of standard operating procedures (SOPs) of four

Fig. 6 Integration of risk assessment with design control activities 16

In addition, the various activities and decisions identified in

interviews. The model is presented in linear-form as a stage-gated

Fig. 7 Total product life cycle 18

Journal of Medical Devices

JUNE 2009, Vol. 3 / 021004-5

occur at different times in the development process depending on

Phase 1/Gate 1:. initiation, opportunity, and risk analysis

It should be noted that although each development phase is

4.1.2.1 Predevelopment activities (phase 0). In order to create

Fig. 9 Linear medical device development model

treat the condition. Next, a preliminary market analysis, financial

nology risk assessment. The IP review includes evaluation of the

Understanding the market for a proposed medical device and

Market analysis/competitive assessment

021004-8 / Vol. 3, JUNE 2009

Transactions of the ASME

new device should be ideally priced and positioned to make the

bution plan, reimbursement plan, sales and distribution plan,

CPT: Current Procedural Terminology

021004-10 / Vol. 3, JUNE 2009

respective countries$ can be applied to a proposed device, and if

DRG: Diagnosis Related Groups

Transactions of the ASME

Phase IV: Deliverables and decision gate

021004-12 / Vol. 3, JUNE 2009

Fig. 11 Design iteration based on failed verifi cation and

design process is design freeze, after which no element of the

Devices tend to be more heterogeneous #see below$ as a

for the different risk-based regulatory pathways for devices is the

Verification and validation activities, outlined in Phases III and

Transactions of the ASME

Journal of Medical Devices

!32" USPTO, 2006, 35 U.S.C. 271 Infringement of Patent, Appendix L http://

JUNE 2009, Vol. 3 / 021004-15

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