Design Controls: Building Objective Evidence and Process Architecture to Meet FDA and ISO Compliance - OMTEC 2018

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Presented by:
MidWest Process Innovation, LLC
Design Controls:
Building Process Architecture using Objective Evidence
21 CFR, Part 820.30
ISO 13485:2016, Section 7.3
Preamble to the QS Regulation

Design Controls
Begins
Concept &
Feasibility
Risk Analysis
Begins
Manufacturing
Design
Review
Design
Review
Design
Review
Require Pilot
Mfring.
Phase
Product
Release
User Needs Verification
Design Validation
Design
Changes
Begin
DHF Begins
Design History File
Marketplace
Post Production
Product
History
Outputs OutputsOutputs
Design
Plan
QRB
Design Processes
Transfer
Inputs
In Continuum
DMR & the
Medical
Device File

From the Preamble
Since early 1984, FDA has identified lack of design controls as one of the
major causes of device recalls. The intrinsic quality of devices, including
their safety and effectiveness, is established during the design phase.
Thus, FDA believes that unless appropriate design controls are observed
during preproduction stages of development, a finished device may be
neither safe nor effective for its intended use. The SMDA provided FDA
with the authority to add preproduction design controls to the device
CGMP regulation.
…as stated, FDA want to emphasize that it expect manufactures to be in
a reasonable state of compliance with the design control requirements
from June 1, 1997, to June 1, 1998, because extra time was given to the
industry for implementing design controls before the final regulation
became effective.
…any FDA inspection observations realized up to June 1, 1998 will be
noted but not enforced...as of June 1, 1998 enforcement consequences
related to compliance issues (21 CFR, Part 820.30) will be in full force.

Design Controls – Applicability and Business Acumen
FDA has added general requirements for design controls to the device CGMP
regulation for all class III and II devices and certain class I devices.
FDA is not subjecting the majority of class I devices to design controls because FDA
does not believe that such controls are necessary to ensure that such devices are
safe and effective and otherwise in compliance with the act.
However, all devices, including class I devices exempt from design controls, must
be properly transferred to production in order to comply with Sec. 820.181, as well
as other applicable requirements.
For most class I devices, FDA believes that the production and other controls in the
new quality system regulation and other general controls of the act will be
sufficient, as they have been in the past, to ensure safety and effectiveness.
Design Strategy and Planning

Scope...Impact on Device Life Cycle…
The QS regulation is in Part 820 of Title 21 of the Code of Federal
Regulations (CFR). This regulation covers (at least):
•quality management and organization
•auditing
•training
•device design
•acceptance activities
•purchasing controls / acceptance activities
•production and process controls and ancillary processes,
•packaging and labeling control,
•device evaluation,
•handling, storage, distribution,
•corrective action and preventive action
•non-conforming product
•complaint handling,
•servicing and installation
•document control and records
•statistical techniques

Concept and Feasibility (Research)
The design control requirements are not intended to apply to the
development of concepts and feasibility studies. However, once it is decided
that a design will be developed, a plan must be established to determine the
adequacy of the design requirements and to ensure that the design that will
eventually be released to production meets the approved requirements.
Design Strategy and Planning

Research vs. Development
Some manufacturers have difficulty in determining where
research ends and development begins. Research activities
may be undertaken in an effort to determine new business
opportunities or basic characteristics for a new product. It
may be reasonable to develop a rapid prototype to explore the
feasibility of an idea or design approach, for example, prior to
developing design input requirements. But manufacturers
should avoid falling into the trap of equating the prototype
design with a finished product design. Prototypes at this stage
lack safety features and ancillary functions necessary for a
finished product, and are developed under conditions which
preclude adequate consideration of product variability due to
manufacturing.

Not a Requirement...”encouraged”
Manufacturers of exempt Class I devices are encouraged to use 820.30,
Design Controls, as guidance
Quality Management System Strategy and Scope

Systematic Life Cycle Approach…Appropriate for Intended Use…Interrelations
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.

…it’s why FDA comes to visit
Quality Management System Strategy and Scope
Note: FDA investigators will not inspect a device under the design control
requirements to determine whether the design is appropriate or safe and
effective. Section 520(f)(1)(a) of the act precludes FDA from evaluating
the safety or effectiveness of a device through preproduction design
control procedures. FDA investigators will evaluate the process, the
methods, and the procedures that a manufacturer has established to
implement the requirements for design controls.

Visibility for Management…Communications…
Cross-functional Team
In practice, design controls provide managers and designers with
improved visibility of the design process. With improved visibility,
managers are empowered to more effectively direct the design
process-that is, to recognize problems earlier, make corrections, and
adjust resource allocations. Designers benefit both by enhanced
understanding of the degree of conformance of a design to user and
patient needs, and by improved communications and coordination
among all participants in the process.

Concept and Feasibility – User Needs
CONCEPT DOCUMENTS VERSUS DESIGN INPUT
In some cases, the marketing staff, who maintain close
contact with customers and users, determine a need for a new
product, or enhancements to an existing product.
Alternatively, the idea for a new product may evolve out of a
research or clinical activity. In any case, the result is a
concept document specifying some of the desired
characteristics of the new product.
Characterize the Device – early stages
Competitor and historical data is important. From verification data and experimentation during R
Human Factors leading to design inputs (requirements phase)
Design Input (needs of user) / verification (output meets input) / Validation (meets user needs)
Human factors’ studies, analysis, testing / User error is still considered a non-conformity

Research → Concept and Feasibility – User Needs
Some members of the medical device community view these
marketing memoranda, or the equivalent, as the design input.
However, that is not the intent of the quality system requirements.
Such concept documents are rarely comprehensive, and should not
be expected to be so.
Rather, the intent of the quality system requirements is that the
product conceptual description be elaborated, expanded, and
transformed into a complete set of design input requirements which
are written to an engineering level of detail.

Concept and Feasibility – User Needs – Your Device
This is an important concept. The use of qualitative terms in a concept
document is both appropriate and practical. This is often not the case for a
document to be used as a basis for design.
■It is not the intent of FDA to interfere with creativity and innovation, and it is
not the intent of FDA to apply the design control requirements to the research
phase. Instead, the regulation requires the establishment of procedures to
ensure that whatever design is ultimately transferred to production is, in fact,
a design that will translate into a device that properly performs according to
its intended use and user needs.
■To assist FDA in applying the regulation, manufacturers should document
the flow of the design process so that it is clear to the FDA
investigator where research is ending and development of
the design is beginning.
Thus, a concept document may be the starting point for development, but it
is not the design input requirement. This is a key principle-the design input
requirements are the result of the first stage of the design control process.

Class I Devices that have, Historically, Presented Health Hazards
…devices included on the Class I list have experienced failures due to
design related problems that have resulted in health hazards,
injuries, or death.
…further, verification, or even validation, cannot provide the
assurance of proper design for some devices, especially those
containing extensive software…all automated devices must be
developed under the design control requirements.

Life-Cycle Approach…Product…Process...”Womb to Tomb”
Design controls are a component of a comprehensive quality
system that covers the life of a device. The assurance process
is a total systems approach that extends from the
development of device requirements through design,
production, distribution, use, maintenance, and eventually,
obsolescence. Design control begins with development and
approval of design inputs, and includes the design of a device
and the associated manufacturing processes.
QRB / Post Design / Documentation / Post Market Surveillance

v versus V...User Needs versus Inputs…Outputs versus Inputs…Review

Design Planning and Responsibility and Authority
FDA requires the plan to describe or reference design activities and
define responsibility for implementing the activities, rather than
requiring that the plan identify each person responsible for carrying
out each activity.
...the FDA does not dictate how or by whom the plan must be
approved. The regulation gives the manufacturer the necessary
flexibility to have the same person(s) who is responsible for the
review also be responsible for the approval of the plan if appropriate.
plans shall be reviewed, updated, and approved as design and
development evolves,'' indicating that changes to the design plan are
expected.
...design plan typically includes at least proposed quality practices,
assessment methodology, recordkeeping and documentation
requirements, and resources, as well as a sequence of events related
to a particular design or design category.

Design Reviews...Stage Gates...Close one door & open another
The design reviews are conducted at strategic points in the design
process – Stage Gates. For example, a review is conducted to assure
that the design input requirements are adequate before they are
converted into the design specifications.
Another is used to assure that the device design is adequate before
prototypes are produced for simulated use testing and clinical
evaluation.
Another, a validation review, is conducted prior to transfer of the
design to production. Generally, they are used to provide assurance
that an activity or phase has been completed in an acceptable
manner, and that the next activity or phase can begin.

Concurrent Engineering... the reality of the “factory floor”
In a traditional waterfall development scenario, the engineering department
completes the product design and formally transfers the design to production.
Subsequently, other departments or organizations develop processes to
manufacture and service the product. Historically, there has frequently been a
divergence between the intent of the designer and the reality of the factory
floor, resulting in such undesirable outcomes as low manufacturing yields,
rework or redesign of the product, or unexpectedly high cost to service the
product.
One benefit of concurrent engineering is the involvement of production and
service personnel throughout the design process, assuring the mutual
optimization of the characteristics of a device and its related processes. While
the primary motivations of concurrent engineering are shorter development
time and reduced production cost, the practical result is often improved
product quality.
Getting everyone involved

Concurrent Engineering – a Design Activity
Concurrent engineering encompasses a range of practices and techniques.
From a design control standpoint, it is sufficient to note that concurrent
engineering may blur the line between development and production.
On the one hand, the concurrent engineering model properly emphasizes that
the development of production processes is a design rather than a
manufacturing activity. On the other hand, various components of a design
may enter production before the design as a whole has been approved.
Thus, concurrent engineering and other more complex models of
development usually require a comprehensive matrix of reviews and
approvals to ensure that each component and process design is validated
prior to entering production, and the product as a whole is validated prior to
design release.
820.50 / 820.80 / 820.70 / 820.72

Concurrent Engineering – Inter-relationships of key functions and people
While the primary motivations of concurrent engineering are shorter
development time and reduced production cost, the practical result is often
improved product quality.

Risk Management...Becomes a Design Input...
Risk management is the systematic application of management policies,
procedures, and practices to the tasks of identifying, analyzing, controlling,
and monitoring risk. It is intended to be a framework within which
experience, insight, and judgment are applied to successfully manage risk.
Risk management begins with the development of the design input
requirements. As the design evolves, new risks may become evident. To
systematically identify and, when necessary, reduce these risks, the risk
management process is integrated into the design process.
...unacceptable risks can be identified and managed earlier in the design
process when changes are easier to make and less costly.

Design Plans and Planning

Design Plans and Planning...basically, a plan
The design planning exercise and execution of the plans are complex because
of the many areas and activities that should be covered. Some of the key
activities can be:
• determining and meeting the user/patients requirements;
• meeting regulations and standards;
• developing specifications for the device;
• developing, selecting and evaluating components and suppliers;
• developing and approving labels and user instructions;
• developing packaging;
• design reviews;
• developing specifications for manufacturing processes;
• verifying safety and performance of prototype and final devices;
• verifying compatibility with the environment and other devices;
• developing manufacturing facilities and utilities;
• developing and validating manufacturing processes;
• training employees;
• documenting the details of the device design and processes
• if applicable, developing a service program.

Design Planning...Standardized...Scope...Intent
More than MS Project / Less Complex & Less Details
To support thorough planning, the QS regulation requires
each manufacturer to establish and maintain plans that
describe or reference the design and development activities
and define responsibility for implementation.
The plans should be consistent with the remainder of the
design controls.
One of the first elements in each design plan should be how
you plan to meet each of the design control requirements
for the specific design you plan to develop; that is, the
design plans should support all of the required design
control activities.

DHF at the Beginning...References...Outputs are the Basis for DMR
The design controls section of the quality system requires a
design history file (DHF) [820.30(j)] that contains or
references the records necessary to demonstrate that the
design was developed in accordance with the:
1. approved design plan, and
2. regulatory requirements.

Design of Product………………...Design of Process
Proactive interface is a important aspect of concurrent
engineering. Concurrent engineering is the process of
concurrently, to the maximum feasible extent, developing
the product and the manufacturing processes together.
A plan developed by a cross-functional team
(not just design engineers)

Simple is more appropriate – Details for specific Purposes
Structure of Plans
Each design control plan should be broad and complete rather
than detailed and complete. The plan should include all
major activities and assignments. Broad plans are:
• easier to follow;
• contain less errors;
• have better agreement with the actual activities; and
• will require less updating than detailed plans.
...put the details into protocols and work instructions
Not Detailed and Complete

Design Change Notice – Authority behind changes
Plans require updating as the development
activities dictate. Thus, the QS regulation
requires in 820.30(a) that
plans shall be reviewed, updated, and approved as
the design and development evolves
changes are considered for validation
and/or verification

Stage-gate...Design History File – Part of the Plan
The details of updating are left to the manufacturer.
The design review meetings are a good time and
place to consider, discuss and review changes
that may need to be made in the design
development plan.

Recap...What a Plan Could Show...
The design and development plan may include a schedule showing
starting and completion dates for each major task, project milestone,
or key decision points. The method chosen and the detail will vary
depending on the complexity of the project and the level of risk
associated with the device.
For small projects, the plan may consist of only a simple flow
diagram or computer spreadsheet. For larger projects, there are a
number of project management tools that are used to develop plans.
Three of the most commonly used are the Program Evaluation and
Review Technique (PERT), the Critical Path Method (CPM), and the
Gantt chart. Software is available in many forms for these methods.
When selecting these tools, be careful to choose one that best fits
the needs of the project.

The Chart(s) Part of the Design Plan

Re-Planning Examples
• Changes in project resources or responsibilities
• Shifts to using external resources
• Schedule slippage
• Milestone changes
• Adoption of new or different technology
used in the device
• Identification of new tasks

A Design Matrix should be developed as soon as there
are approved design inputs

Design Input – Requirements Phase
FDA emphasizes, however, that the section requires the manufacturer to
ensure that the design input requirements are appropriate so the device
will perform to meet its intended use and the needs of the user.
In doing this, the manufacturer must define the performance
characteristics, safety and reliability requirements, environmental
requirements and limitations, physical characteristics, applicable
standards and regulatory requirements, and labeling and packaging
requirements, among other things, and refine the design requirements
as verification and validation results are established.
Design inputs are commonly quantitative and measurable

When is Design Input Established?
Design Inputs Approved
(User Needs) (Design Input)
Development
Begins
User
Needs
End
Research Development

Users are a manufacturer’s intended segment of the population that
will interact with a device. A device may have more than one type of
user, such as:
- Medical professionals (with particular skills)
- Caregivers
- Installers, maintenance & cleaning personnel
- Patients
- Patients are users who are also directly affected by device performance
User needs are the particular expectations a user group has relative
to the device’s purpose and function

Design Input
the physical and performance requirements of a device that
are used as a basis for device design
820.3(f)
The term “requirement” is meant in the broadest sense, to
encompass any internally or externally imposed requirements
such as safety, customer-related, and regulatory
requirements. All of these requirements must be
considered as design inputs.
Preamble #19

Verification Method – e.g. the Traceability Matrix
Another self-documenting verification method is the traceability
matrix. This method is particularly useful when the design input and
output are both documents; it also has great utility in software
development.
In the most common form of the traceability matrix, the input
requirements are enumerated in a table, and references are provided
to each section in the output documents (or software modules) which
address or satisfy each input requirement.

Design Input(s) include the Procedures (process) that
Driver Design Controls in your QMS
FDA agrees that procedures for ensuring appropriate design controls are of the
utmost importance and has modified the section to clarify that the manufacturer
must establish and maintain procedures to ensue that the design requirements are
properly addressed. FDA requires the manufacturer to establish and maintain
procedures to control the design of the device in order to ensure that specified
design requirements are met. It should be emphasized that the input itself must also
be appropriate; the requirement is for the procedures to be defined, documented,
and implemented. Thus, if the input requirements related to a device fail to address
the intended use of the device, for example, the manufacturer has failed to comply
with the provision.
Design controls for the device and for building the design controls process

The Effective Development of Design Input(s)
...care must be exercised in applying this principle. Effective
development of design input requirements encompasses input from
both the product developer as well as those representing the needs
of the user, such as marketing.
Terminology can be a problem. In some cases, the product
conceptual description may be expressed in medical terms. Medical
terminology is appropriate in requirements when the developers and
reviewers are familiar with the language, but it is often preferable to
translate the concepts into engineering terms at the requirements
stage to minimize miscommunication with the development staff.
Joy Stick has a full range of motion → 360 degrees of motion

Informational Inputs and Responsibilities - Marketing
Marketing shall plan and conduct all customer contacts to
obtain information on customer desires, needs, expected
pricing, opinions about existing devices, the competition,
etc.
Market research results are to be documented and marked
confidential.

Process Inputs and Responsibilities - examples
RESPONSIBILITY
Marketing and Engineering have the primary responsibility for
determining safety and performance requirements and developing
input specifications; however, all departments (process owners) are
expected to support the development of process input requirements
and subsequent specifications (outputs).
Quality Control Process___Develop Sampling Plans using ISO 2859 / 3951
Purchasing Process ____ Evaluate Perspective Suppliers using IMDRF Guidance
Manufacturing Process_______________________?
Labeling Control Process______________________?
Packaging Control Process____________________?
Pre-Clinical Process __Apply Human Factors / Usability Engineering using ANSI/AAMI 62366
Distribution Process__________________________?
Machine Qualification Process__________________?
DHF→DMR→DHR Process_____________________?
Risk Management Process_____________________?
International Medical Device Regulators Forum (IMDRF)

Specify what the Design is Intended to Do
Some examples should clarify this point. A basic principle is that
design input requirements should specify what the design is intended
to do while carefully avoiding specific design solutions at this stage.
For example, a concept document might dictate that the product be
housed in a machined aluminum case. It would be prudent for
product developers to explore why this type of housing was specified.
Perhaps there is a valid reason-superior electrical shielding,
mechanical strength, or reduced time to market as compared to a
cast housing. Or perhaps machined aluminum was specified because
a competitor's product is made that way, or simply because the user
didn't think plastic would be strong enough.

Incorrect Assumptions - Discussion
Not all incorrect assumptions are made by users. Incorrect
assumptions made by product developers may be equally
damaging. Failure to understand the abuse to which a
portable instrument would be subjected might result in the
selection of housing materials inadequate for the intended use
of the product.
What do you do to better understand what is really needed?
Wheelchair
Stent

Design Inputs Requirements must be Comprehensive
Design input requirements must be comprehensive. This may
be quite difficult for manufacturers who are implementing a
system of design controls for the first time. Fortunately, the
process gets easier with practice.
How do you know when to quit adding inputs?
___________?
___________?
___________?
___________?

Design Input Categories
It may be helpful to realize that design input requirements fall
into three categories. Virtually every product will have
requirements of all three types:
1/ Functional requirements specify what the device does, focusing on
the operational capabilities of the device and processing of inputs
and the resultant outputs.
Wheelchair
Stent

It may be helpful to realize that design input requirements fall
into three categories. Virtually every product will have
requirements of all three types:
2/ Performance requirements specify how much or how well
the device must perform, addressing issues such as speed,
strength, response times, accuracy, limits of operation, etc.
This includes a quantitative characterization of the use
environment, including, for example, temperature, humidity,
shock, vibration, etc.
Requirements concerning device reliability and safety also fit
into this category.
Wheelchair
Stent

It may be helpful to realize that design input requirements fall into
three categories. Virtually every product will have requirements of all
three types:
3/ Interface requirements specify characteristics of the device which
are critical to compatibility with external systems; specifically, those
characteristics which are mandated by external systems and outside
the control of the developers. One interface which is important in
every case is the user and/or patient interface.
Performance Standards are already set in place...
Competitor’s products have these functional features...
Foldable wheelchair can only fit in certain vehicles...
Wheelchair
Stent

The Scope of the Design Input Requirements
What is the scope of the design input requirements
development process and how much detail must be provided?
The scope is dependent upon the complexity of a device and
the risk associated with its use. For most medical devices,
numerous requirements encompassing functions,
performance, safety, and regulatory concerns are implied by
the application. These implied requirements should be
explicitly stated, in engineering terms, in the design input
requirements.
Wheelchair
Stent

What Level of Detail is Required
Determining the appropriate level of detail requires
experience. However, some general guidance is possible. The
marketing literature contains product specifications, but these
are superficial. The operator and service manuals may contain
more detailed specifications and performance limits, but these
also fall short of being comprehensive.
Wheelchair
Stent

...for example
Some insight as to what is necessary is provided by examining the requirements for a
very common external interface.
For the power requirements for AC-powered equipment, it is not sufficient to simply say
that a unit shall be AC-powered.
It is better to say that the unit shall be operable from AC power in North America,
Europe, and Japan, but that is still insufficient detail to implement or validate the design.
If one considers the situation just in North America, where the line voltage is typically
120 volts, many systems are specified to operate over the range of 108 to 132 volts.
However, to account for the possibility of brownout, critical devices may be specified to
operate from 95 to 132 volts or even wider ranges.
Based on the intended use of the device, the manufacturer must choose appropriate
performance limits.
Cross-functional teams must work together...brainstorming

...30% of the Total Project Time
For complex designs, it is not uncommon for the design input
stage to consume as much as thirty percent of the total
project time. Unfortunately, some managers and developers
have been trained to measure design progress in terms of
hardware built, or lines of software code written. They fail to
realize that building a solid foundation saves time during the
implementation. Part of the solution is to structure the
requirements documents and reviews such that tangible
measures of progress are provided. Build in updates.

...and yet again!
At the other extreme, many medical devices have very simple
requirements. For example, many new devices are simply
replacement parts for a product, or are kits of commodity
items (like convenience kits). Typically, only the packaging
and labeling distinguishes these products from existing
products. In such cases, there is no need to recreate the
detailed design input requirements of the item. It is
acceptable to simply cite the predecessor product
documentation, add any new product information, and
establish the unique packaging and labeling requirements.

Assessing Design Input Requirements
Any assessment of design input requirements boils down to a matter of
judgment. It is important for the review team to be multidisciplinary and to
have the appropriate authority. A number of criteria may be employed by the
review team.
Design input requirements should be unambiguous. That is, each requirement
should be able to be verified by an objective method of analysis, inspection,
or testing. For example, it is insufficient to state that a catheter must be able
to withstand repeated flexing. A better requirement would state that the
catheter should be formed into a 50 mm diameter coil and straightened out
for a total of fifty times with no evidence of cracking or deformity.
A qualified reviewer could then make a judgment whether this specified test
method is representative of the conditions of use.

review team.
Quantitative limits should be expressed with a measurement tolerance. For
example, a diameter of 3.5 mm is an incomplete specification. If the diameter
is specified as 3.500 ±0.005 mm, designers have a basis for determining how
accurate the manufacturing processes have to be to produce compliant parts,
and reviewers have a basis for determining whether the parts will be suitable
for the intended use.

review team.
The environment in which the product is intended to be used should be
properly characterized. For example, manufacturers frequently make the
mistake of specifying "laboratory" conditions for devices which are intended
for use in the home. Yet, even within a single country, relative humidity in a
home may range from 20 percent to 100 percent (condensing) due to
climactic and seasonal variations. Household temperatures in many climates
routinely exceed 40 °C during the hot season. Altitudes may exceed 3,000 m,
and the resultant low atmospheric pressure may adversely affect some kinds
of medical equipment. If environmental conditions are fully specified, a
qualified reviewer can make a determination of whether the specified
conditions are representative of the intended use.
What about devices that go to war zones?

review team.
When industry standards are cited, the citations should be reviewed for
completeness and relevance. For example, one medical device manufacturer
claimed compliance with an industry standard covering mechanical shock and
vibration. However, when the referenced standard was examined by a
reviewer, it was found to prescribe only the method of testing, omitting any
mention of pass/fail criteria. It was incumbent on the manufacturer in this
case to specify appropriate performance limits for the device being tested, as
well as the test method.
Motorized Wheelchair has to operate in all types of environments
45 Performance Standards

Verification Activities will “tell the tale”
It is almost inevitable that verification activities will uncover
discrepancies which result in changes to the design input
requirements. There are two points to be made about this.
The First Point
...is that the change control process for design input
requirements must be carefully managed. Often, a design
change to correct one problem may create a new problem
which must be addressed. Throughout the development
process, it is important that any changes are documented and
communicated to developers so that the total impact of the
change can be determined. The change control process is
crucial to device quality.

Verification Activities will “tell the tale”
The Second Point
...is that extensive rework of the design input requirements
suggests that the design input requirements may not be
elaborated to a suitable level of detail, or insufficient
resources are being devoted to defining and reviewing the
requirements. Managers can use this insight to improve the
design control process. From a design control perspective, the
number of requirements changes made is less important than
the thoroughness of the change control process.

Input Criteria toward understanding the requirements
After the concept of the new device design is established, the
following basic design input questions should have been
answered:
1. What is the real need for the new device?
2. Where will the new device be used?
3. Who will use the new device?
4. How will the new device be used?
5. With what devices will the new device be used?
6. How long will the new device be used? and
7. Other questions related to the specific device to be developed.
Let’s take your device and answer these six questions_________?

Inputs → Engineering Drawings → Production Drawings
A set of design input requirements, when converted
to engineering terminology, finalized and
accepted as part of the device master record is
called a device or product specification.

Not necessarily a stake in the sand...in continuum to a point
The design input phase usually is in continuum (to
a point) because intensive and formal input
requirements activities usually occur near the
beginning of the feasibility phase and continue to
the early physical design activities.

Example: Simple Design Matrix
Patient Monitor
Discuss Design Validation
User Need Design Input Design Output Design Verification
Portable
Instrument
• Dimensions no greater than
18.0” x 13.0” x 7.5”
• Weight = less than 11.5 lbs
Housing Drawing #765-003
Monitor Specification #763-124
Measure the Housing
Weigh the parts and weigh the
entire instrument
• Can be carried with one
gloved or bare hand
Handle Assembly Drawing #59-02 Measure the handle size
Used in a USA MD’s
Office
Operates on US Standard
Electrical Voltage
Electrical Plug Specification #77
Transformer Specification # V89 Measure the Voltage output
110-volt AC (110V) or 220-volt
AC (220V)

Checklists...Formalized...Specific to Device Type
To reduce the probability of a requirement or
characteristic being left out, a specification
checklist may be used during the design input
phase. A checklist should be developed that is
broad based but also germane to the product line
of the manufacturer. If used, a checklist should
be part of a standard operating procedure such
as a Design Input Specification Procedure.

Re-Cap- Documented and Authorized...Linkages
The design input requirements shall be documented
and shall be reviewed and approved by a
designated individual(s). The approval, including
the date and signature of the individual(s)
approving the requirements, shall be
documented.

Establish Design Requirements as early as possible
The device specification will undergo changes and
reviews as the device design evolves. However,
one goal of market research and initial design
reviews is to establish complete device
requirements and specifications that will
minimize subsequent changes.

DHF
Old versions of the input requirements and later the
input specifications are put in the design history
file (DHF) or indexed in the computer as part of
the DHF to help show that the design plan was
followed.
The DHF hasn’t been addressed since the beginning of the
project, six months ago. Employees insist that they have all
of the required documentation in their files and will hand
everything over to the document control process owner
right before transfer.

Design Changes
Preamble 52621, Comment #s 87 → 89
...all changes must be (at least) verified prior to making the
change.
...changing the user need or the intended use could require a
revalidation.

Separate from the Change Control in the QMS
DESIGN CHANGES
■ Changes to a design element are controlled per
820.30(i) Design Changes which states that:
each manufacturer shall establish and maintain
procedures for the identification, documentation,
validation or where appropriate verification,
review, and approval of design changes before
their implementation.

Steady State...Product Changes
Most of the details of the change control system are
left to the manufacturer to develop, document
and implement. As the design activity progresses
toward the final stage, it is expected that the
degree of change control will decrease for the
product and increase for the process.

Application of Document and Change Controls to Design
The design control system has to be concerned with
the creation and revision of documents, as well as
the management of finished documents. Additional
mechanisms are required to provide needed
flexibility while preserving the integrity of design
documentation.
What flexibility does your company have in the ECR
Process (Changes during design)?___________

Document Control and Change Control
There are two principal administrative elements involved in
controlling design changes:
• Document control-enumeration of design documents, and tracking
their status and revision history. Throughout this section, the term
"document" is used in an inclusive sense to mean all design
documents, drawings, and other items of design input or output which
characterize the design or some aspect of it.
→Your method during design
• Change control-enumeration of deficiencies and corrective actions
arising from verification and review of the design, and tracking their
resolution prior to design transfer.
→Your method after design crosses over the bridge (to manufacturing)

Design Changes - Discussion
For a small development project, an adequate process for managing
change involves little more than documenting the design change,
performing appropriate verification and validation, and keeping
records of reviews. The main objectives are ensuring that:
1. corrective actions are tracked to completion
2. changes are implemented in such a manner that the original
problem is resolved and no new problems are created; or if
new problems are created, they are also tracked to resolution
3. design documentation is updated to accurately reflect the
revised design.

The life of the design can continue until of “end-of-
device life”*
Those elements of the design that have been verified and
accepted obviously should be under change control.
A design that is released for production should have been
under design and (then) general change control used
in the QMS.
*...and beyond

Document Control
How does this work in Design?
The features of a manufacturing document control system typically include the following:
■Documents should be identified (i.e., named and numbered) in accordance with some
logical scheme which links the documents to the product or component they describe or
depict and illuminates the drawing hierarchy.
■A master list or index of documents should be maintained which presents a
comprehensive overview of the documentation which collectively defines the
product and/or process.
■Approval procedures should be prescribed which govern entry of documents
into the document control system.
■A history of document revisions should be maintained.
■Procedures for distributing copies of controlled documents and tracking their
location should be prescribed.
■A person or persons should be assigned specific responsibility to oversee and carry out
these procedures. It is desirable that the document control system be administered by a
person who is not directly involved with developing or using the documents. For a small
manufacturer, document control might be a part-time job for a technician or clerical staff
person. More typically, one or more librarians or full-time clerical or paraprofessional
employees are required to administer the system.
■There should be a procedure for removal and deletion of obsolete documents.

Change Control
How is this Communicated to all applicable people?
Can anyone make changes without using the “NORMAL” channels?
■ Change requests and change orders should be communicated to
all persons whose work might be impacted by the change.
■ It may not be practical to immediately revise documents affected
by a change order. Instead, the common practice is to distribute
and attach a copy of the change order to each controlled copy of
the original document.
■ Change control procedures should incorporate review and
assessment of the impact of the design change on the design
input requirements and intended uses.
■ A mechanism should be established to track all change requests
and change orders to ensure proper disposition.
■ Change control procedures are usually administered by the
document control staff.

Re-verify and / or Re-Validate the Change
It is important that the design change procedures always
include re-verifying and re-validating the design. Fortunately,
most design changes occur early in the design process, prior
to extensive design validation. Thus, for most design changes,
a simple verification is all that is required.
The later in the development cycle that the change occurs, the
more important the validation review becomes.
Why is that?________

Changes to Product...to Process...Exercise
Request for Change in Manufacturing - Product Specification – 7.013+/-.001 to
7.013+/-.01 mm
Adding new warning statements to IFU because of trend, re; similar complaints
(MDRs) received - involved with injury to patients
Add a new design input having to do with human factors (concerning the nursing
staff and physicians) – Note: design inputs were frozen over five months ago
Request for Change right before the pilot run used for producing product for design
validation efforts - Product Specification – 7.013+/-.001 to 7.013+/-.01 mm
The PFMEA hasn’t been revised in 9 months...new occurrence data forces corrective
action to account for reoccurring defectss concerning burrs on metal parts
The essential outputs have been finalized some time ago. A critical supplier for the
drug used on drug coated stents is going out of business at the end of next quarter.

Design Review
Pre-Amble 52619, Comment #80

Design Review Occurs Throughout the Design Effort
User
Needs
Design
Process
Design
Input
820.30(c)
Design
Output
820.30(d)
Medical
Device
Design
Verification
820.30(f)
Design Review
820.30(e)
Design
Validation
820.30(g)

Stage-gate...Cross-functional thinking...third party
Design review [820.30(e)] is one of the key design
control elements in a quality system. The
objectives of design review are stated in the
definition of design review in 820.3(h) as follows:
Design review means a documented,
comprehensive, systematic examination of a
design to evaluate the adequacy of the design
requirements, to evaluate the capability of the
design to meet these requirements, and to
identify problems.

Discussion
The nature of reviews changes as the design progresses.
During the initial stages, issues related to design input
requirements will predominate.
Next, the main function of the reviews may be to evaluate or
confirm the choice of solutions being offered by the design
team. Then, issues such as the choice of materials and the
methods of manufacture become more important.
During the final stages, issues related to the verification,
validation, and production may predominate.

Discussion
The term "review" is commonly used by manufacturers to describe a variety
of design assessment activities. Most, but not all, of these activities meet the
definition of formal design reviews. The following exceptions may help to
clarify the distinguishing characteristics of design reviews.
■Each design document which constitutes the formal output, or deliverable, of
a design task is normally subject to evaluation activities, sometimes referred
to as informal peer review, supervisory review, or technical assessment.
These activities, while they may be called reviews, are often better described
as verification activities, because they are not intended to be comprehensive,
definitive, and multidisciplinary in their scope. Rather, their purpose is to
confirm that design output meets design input.
■Verification activities affect and add to the design output, and are themselves
subject to subsequent design review.

Discussion
The term "review" is commonly used by manufacturers to
describe a variety of design assessment activities. Most, but
not all, of these activities meet the definition of formal design
reviews. The following exceptions may help to clarify the
distinguishing characteristics of design reviews.
Developers may conduct routine or ad hoc meetings to discuss
an issue, coordinate activities, or assess development
progress. Decisions from such meetings may not require
formal documentation; however, if a significant issue is
resolved, this should be documented. If the outcome results in
change to an approved design document, then applicable
change control procedures should be followed.
A “hallway” meeting forces a specification to
change...now what?

Design Reviews in the Design Plan
Control of the design review process is achieved by developing
and implementing a formal design review program consistent
with quality system requirements. The following issues should
be addressed and documented in the design and development
plan(s).
• Number and Type of Reviews
• Selection of Reviewers
• Design Review Procedures (Logistics)
• Relationship of Design Review to Verification and Validation...In
practice, design review, verification, and validation overlap one
another, and the relationship among them may be confusing. As a
general rule, the sequence is: verification, review, validation, review.

Relationship of Design Review to Verification and Validation
In most cases, verification activities are completed prior to the
design review, and the verification results are submitted to the
reviewers along with the other design output to be reviewed.
Similarly, validation typically involves a variety of activities, including
a determination that the appropriate verifications and reviews have
been completed.
Thus, at the conclusion of the validation effort, a review is usually
warranted to assure that the validation is complete and adequate.

Design Reviews...Formalized...Planned...Changes
To meet the systematic design review requirement, device
design and design reviews should progress through defined
and planned phases starting with the design input phase
and continuing through validation of initial production units
or lots.
Subsequent activities are usually design changes.

Assessments...Product Audits...Process Audits
To meet the design review comprehensive requirement,
assessments should include a formal review of the main
device and subsystems, including accessories, components,
software, labeling and packaging; production and resource
needs; and installation and service, if needed.
Can FDA look at the minutes from Management Reviews?
Can FDA look at the minutes from QRB Meetings?
Can FDA look at the minutes from Design Reviews?
Can FDA look at the minutes from Staff Meetings?
Can FDA look at the agenda for Management Reviews?
Can FDA look at notes that you keep concerning a project?
Can FDA look at laboratory notebooks?
If an employee takes a laboratory notebook with a lot of information
home and then loses it in the trash collection, what do you do?

S/E...progressing to...Manufacturability
Thus, the reviews of the design input and the design should
extend beyond merely satisfying user-stated requirements in
order to assure that safety and effectiveness goals are met.
As the development process progresses, the reviews should
cover producibility and production documentation such as
assembly drawings, manufacturing instructions, test
specifications, test procedures, etc.

Applications...Focused...Classification
The extent and frequency of design reviews depends on the
complexity and significance of the device being evaluated.
What could the first design review cover, subject-wise?
What could the last design review cover, subject-wise?
Design verification on a critical part is failing – what would the
discussion at the design review entail?
You need 500 devices for a design validation study – what
would the discussion at the design review entail?

Vehicle for Inputs...Internal...External...Clinical Use
When the design process is a redesign of an existing device, a
special effort should be made to assure that data obtained
from previous failures, complaints, and service records are
made available and reviewed by those responsible for
design, design input and design review.
How does this happen at your company?

Scheduled in the Design Plan...Agenda...Resources
Preparation For Reviews
The designated moderator or other designated employee
should announce the formal review meetings with appropriate
lead time and include an agenda.

Prepare...Distribute...Prepare...Simplicity
Persons who are making presentations should prepare and
distribute information to help clarify review issues and help
expedite the review. However, the intent of the quality
system is not that presentations be so formal and elaborate
that designers are spending excessive time on
presentations rather than on designing a safe and
effective device.

Design Reviews for Learning and Sharing Ideas
Persons who plan to attend a review meeting should come
prepared to discuss the key issues on the agenda and
issues related to the current design phase. Design review
meetings are a great educational forum...
Don’t forget the deliverables...

The Design Review can open and close gates
However, design review meetings should not be used as a
primary tool to educate or bring new employees or
unprepared employees up-to-speed. To do so detracts from
the intent of the meeting and detracts from the intent of
the GMP requirements.
The president of Company X does not get involved with daily
design controls operations or manufacturing operations for
that matter. Every time she comes to design reviews and
pre-production planning meetings she wants to be brought
up to speed and is never satisfied with timing issues,
product produced without defects, not having the right
people in place “to make it happen.” What do we do??

Agenda...Minutes...Design Changes...Transfer
Design reviews are conducted for design definition,
selection and adequacy; communication and
resolution of problems and issues.

Resolve conflicts…objective evidence…not just
“chatter”
The design review of the initial requirements allows input from
all parties. Various people may participate and "buy in" or
"become part of the process."
As the design input and review activities progress, any
conflicts are resolved and the preliminary specifications for
the device, accessories, labeling, and packaging are
established.

Design Reviews – Importance and ROI
Design reviews reduce errors, help avoid problems, help find
existing problems, help propose solutions, increase
producibility and reduce production transfer problems.
The relentless inquiry during design reviews will expose
needed design input requirements and/or design
corrections that otherwise may have been overlooked.

Full Process Reviews...Sub-process Reviews
Design review meetings may be grouped into two
levels such as:
1. total or major program review meetings, and
2. sub-program or team review meetings.

Interface Requirement....Satisfy the QMS Requirements
Some of the review meetings need to be total or major
program review meetings, because this is the only type of
review meeting that will satisfy all of the GMP review
requirements, particularly the interface requirement for
interaction between or among different organizational
groups.

Open Conversation...Cross-Functional...Third Party
Sub-program, team and contractor review meetings that are
design review meetings, are subject to quality system
design controls, and should be conducted in a manner that
meets the GMP requirements. Sub-program or team
meetings are encouraged, as these can be very effective
and efficient in reviewing and resolving sub-program
issues.
How do the minutes from these sub-reviews become part of
the “big picture”?
How do you store and retain the minutes from major reviews
conducted throughout the design process?
After the product is released, do we need to conduct reviews?

Design History File...Start Early, re; compilation
The records of total program and team meetings are part of
the device design history file. The team review records or a
summary of team records and the current design
documentation are to be available, as appropriate, at total
program review meetings

Informal Meetings can be inputs to Formal Meetings
Design review meetings are called under two scenarios:
----- first are the meetings that are preplanned
and called at least on a per design phase;
----- second are ad hoc meetings that are covered in the broad
plans and are called to review or resolve a specific problem or issue.
The preplanned design review meetings and ad hoc meetings are
part of the planning and interaction that are required in 820.30(b),
Design and Development Planning.

21 CFR, Part 820
Reasonable notes and copies of significant engineering
documents discussed during total device system, ad hoc,
contractor, and other review meetings are part of the
device design history file.

Formal Meetings...Periodic...Planned...Agenda
There are four requirements related to design reviews:
1. The meetings should be formal. That is, key attendees are
designated and the meetings are conducted at least once per
stage/phase, are planned, are announced or are periodic,
have an appropriate agenda, notes are recorded, etc.,
according to the manufacturer procedure for design reviews.

Knowledgeable Personnel...Objective...Unbiased
2. To meet the definition of design review in 820.3(h), the review
should include persons who are intimately knowledgeable about
the technical characteristics of the design such as performance,
safety, compatibility, etc. In many manufacturers this can only be
done by those persons responsible for the design.
However, reviews are to be objective, unbiased examinations by
appropriately trained personnel which should include an
individual(s) not responsible for the design. The moderator of the
review meeting may be one of the persons not responsible for the
design.

Pre and Post Design Review(s)
3. Pre- and post-review meeting significant responsibilities and
assignments should be documented [820.30(b)]. These
assignments are not unusual -- they are simply ordinary work
required to develop a new product or modify an existing product.
The progress and/or results of such assignments would typically
be reported at the next review meeting. Documentation is not
required for detailed day-to-day development activities that are
part of the designer’s routine job.

DHF...Minutes...Plans were followed...or not
4. The design review meeting results are made a part of the device
design history file. The results should include minutes and should
include notes, or annotated draft drawings and annotated draft
procedures that played a significant role during the design review.
Such documents help show that plans were followed,
verification/validation was reviewed, and, to some extent,
how the design evolved.

Examples only...Depends upon the Scope of the Project
Resources...Changes...Formalized
The device design review meeting minutes should include
information such as:
• moderator and attendees,
• date and design phase/stage,
• plans and/or agenda,
• problems and/or issues to identify and solve,
• minutes and reports, and
• follow-up report(s) of solutions and/or the next review covers the
solutions and remaining issues.

Forms ?
Manufacturers may use a form to capture some of this
information for minutes such the device, date, moderator,
attendees, major phase, problems, assignments, etc.
The device design review minutes are a key and required part
of the design history file.

Ideally, coordinated effort...Design Review...Stages
Initial production and subsequent validation are
well defined stages; and, therefore, design
review(s) shall be performed as required by
820.30(e), Design Review.
The design validation of initial production should be
followed by a "final" design review to meet the
design review requirement.
Hold a design review – Preparation / Logistics / Players / Agenda (topics) / Minutes
ISSUE – Re: Balloon inflation / deflation times are not meeting specifications, i.e. the balloon
must inflate and deflate in a short enough time to minimize obstruction of blood
flow (Specification is < 10 seconds for inflation and < 20 seconds for deflation –
results are 20% higher than specification as stated)

Design Changes...Validation too early...Successful
If the validation of the final design and subsequent design
review(s) reveal design problems, then design changes are
required to correct these problems.
Design changes require another design verification and, where
appropriate, validation and review of all parts or the
affected parts of the device system.

Design Outputs
Preamble Page 52619, Comments 76 - 78

Definitions
820.3(g) Design output means the results of a design effort at
each design phase and at the end of the total design effort.
The finished design output is the basis for the device master
record. The total finished design output consists of the device,
its packaging and labeling, and the device master record.
820.3(y) Specification means any requirement with which a
product, process, service or other activity must conform.

Output...SOP...Acceptance Criteria...Approved
To generate the design output per the QS
regulation in 820.30(d), three activities are
required. Each of these is listed and discussed
below.
1. Each manufacturer shall establish and maintain procedures for
defining and documenting design output in terms that allow an
adequate evaluation of conformance to design input
requirements.
2. Design output procedures shall contain or make reference to
acceptance criteria and ensure that those design outputs that
are essential for the proper functioning of the device are
identified.
3. Design output shall be documented, reviewed, and approved
before release. The approval, including the date and signature
of the individual(s) approving the output, shall be
documented.

Discussion
The quality system requirements for design output can be separated
into two elements: Design output should be expressed in terms that
allow adequate assessment of conformance to design input
requirements and should identify the characteristics of the design
that are crucial to the safety and proper functioning of the device.
This raises two fundamental issues for developers:
• What constitutes design output?
• Are the form and content of the design output suitable?
• Give me three examples of design outputs that could be under revision
control during design but not subsequently under revision control in
manufacturing?

Discussion...continued
The first issue is important because the typical development project produces
voluminous records, some of which may not be categorized as design output.
On the other hand, design output must be reasonably comprehensive to be
effective.
As a general rule, an item is design output if it is a work product, or
deliverable item, of a design task listed in the design and development plan,
and the item defines, describes, or elaborates an element of the design
implementation. Examples include block diagrams, flow charts, software high-
level code, and system or subsystem design specifications.
The design output in one stage is often part of the design input in
subsequent stages.
Design output includes production specifications as well as descriptive
materials which define and characterize the design.

For Example, Production Specifications
Production specifications include drawings and documents used to procure
components, fabricate, test, inspect, install, maintain and service the device,
such as the following:
• assembly drawings
• component and material specifications
• production and process specifications
• work instructions
• quality assurance specifications and procedures
• installation and servicing procedures
• packaging and labeling specifications, including methods and
processes used

Other Descriptive Materials can be Outputs
■ Other design output items might be produced which are necessary
to establish conformance to design input requirements, but are
not used in its production. For example, for each part which is
fabricated by computer-aided machine, there should be an
assembly drawing which specifies the dimensions and
characteristics of the part. It is a part of the design output
because it establishes the basis for the machine tool program
used to fabricate the part. Other examples of design output
include the following:
• the results of risk analysis
• results of verification activities
• biocompatibility test results
• Bio-burden test results

Form and Content
Manufacturers must take steps to assure that the design output characterizes
all important aspects of the design and is expressed in terms which allow
adequate verification and validation. Two basic mechanisms are available to
manufacturers to accomplish these objectives.
First, the manufacturer proactively can specify the form and content of design
output at the planning stage. For some types of design output, form and
content may be codified in a consensus standard which can be referenced. In
other cases, a manufacturer could specify the desired characteristics, or even
simply specify that the form and content of an existing document be followed.
Second, form and content can be reviewed retroactively as a part of the
design verification process. For example, the verification of design output
could include assessing whether specified documentation standards have
been adhered to.
What information do your component drawings in design contain?
What information do your component drawings in manufacturing (post
design) contain

DHF → basis for the DMR
Design output per 820.3(g) means the results of a design
effort at each design phase and at the end of the total
design effort. The finished design output is the basis for the
device master record. The total finished design output
consists of the device, its packaging and labeling, and the
device master record.
Objective evidence is:
■ A validated process
■ Qualified machines
■ Competent people

Stage gate...drawings to drawings...meet inputs
The design outputs at each phase are documents and physical
design elements that are either complete or are used to
move the design effort into the next phase.
For example, the first design output will usually be the design
requirements document.
What will this document look like...contain...signed off by?

Concept and Feasibility...Condense Requirements
From the requirements and their engineering knowledge, the
designers will derive the preliminary design specifications.
Then the physical design begins.

Starting early to qualify suppliers and components...
For example, the designers may begin the selection of known routine
components that are part of the design and begin documenting
their purchasing and acceptance requirements documented to
meet 820.50 Purchasing Controls
(b)Purchasing Data which requires that each manufacturer shall
establish and maintain data that clearly describe or reference the
specified requirements, including quality requirements, for
purchased or otherwise received product and services
List of objective evidence?
____________________
____________________
____________________
____________________
____________________

Acceptance Activities….Testing….Disposition...Status
The design output for some special or new
components, or components in unusual
applications, will include verification protocols,
purchasing and acceptance requirements
Design Transferred
Incoming Inspection ________ ________
WIP Inspection ________ ________
Finished Product Inspection ________ ________

Product...Process...Objective Evidence...QA
Many of the design output documents are documents that
directly form part of the DMR. The remaining DMR
documents are created by quality assurance, production
engineering, process engineering, technical writing,
installation and servicing, etc.,
...using design output data and information

Incrementally achieved throughout design controls
When all of these design and documentation activities are
completed, the DMR is (can be) summarily completed.
When the DMR is complete and initial production units,
including packaging, meets all specifications, the total
finished design output exists.

Engineering Specification...Verification...Data
Documenting design output in terms that allow an adequate evaluation of
conformance to design input requirements is a significant requirement and
design activity. A common technique for achieving this conformance is
listed below.
• Convert the general input requirements to specific design engineering
specifications and give each item a line/paragraph number.
• Develop the design to meet all of the parameters and characteristics in
the design engineering specification.
• Generate a verification requirement document(s) and test method(s)
for the design and give each requirement/parameter/characteristic the
same line/paragraph number that it has in the design engineering
specification.
• Generate a verification data form that lists each
requirement/parameter/characteristic and give each
requirement/parameter/characteristic the same line/paragraph
number that it has in the design engineering specification.

Cross-functional Review...Authorization and
Responsibility...
Design Output Approval
The third and final output requirement is that: design output shall be
documented, reviewed, and approved before release. The approval,
including the date and signature of the individual(s) approving the output,
shall be documented. This means that:
• Manufacturers may choose to have a group review certain documents and have
individuals review other documents.
• Output documents that are directly part of the DMR are reviewed, dated and
signed by the author which is current practice; and reviewed, dated and
approved by individual(s) designated by the manufacturer. As appropriate, these
reviews should cover technical issues as well as adequacy for use in production,
purchasing, servicing, etc.
• Design output reports, data and any other document that will be used to create
documents in the DMR are reviewed, dated and signed by the author which is
current practice; and reviewed, dated and approved by individual(s) designated
by the manufacturer.

Design Verification and Validation
Preamble Page 52619, Comments 157→ 184

Important Definitions
820.3(y) Specification means any requirement with which a product,
process, service, or other activity must conform.
820.3(z) Validation means confirmation by examination and provision of
objective evidence that the particular requirements for a specific intended use
can be consistently fulfilled.
Process Validation means establishing by objective evidence that a process
consistently (repeatable) produces a result or product meeting its
predetermined specifications.
Design Validation means establishing by objective evidence that device
specifications conform with user needs and intended use(s).
820.3(aa) Verification means confirmation by examination and provision of
objective evidence that specified requirements have been fulfilled.

Discussion
Verification and validation are associated concepts with very
important differences. Various organizations have different
definitions for these terms. Medical device manufacturers are
encouraged to use the terminology of the quality system
requirements in their internal procedures.

SOP...Output meets Input Requirements...
Objective Evidence
DESIGN VERIFICATION
Each manufacturer shall establish and maintain procedures for
verifying the device design. Design verification [820.30(f)] shall
confirm that the design output meets the design input
requirements. The results of the design verification, including
identification of the design, method(s), the date, and the
individual(s) performing the verification, shall be documented in
the DHF.
Verification means confirmation by examination and provision of
objective evidence that specified requirements have been fulfilled.

Discussion – Verification – Building Design Analogy
To illustrate the concepts, consider a building design
analogy. In a typical scenario, the senior architect establishes
the design input requirements and sketches the general
appearance and construction of the building, but associates or
contractors typically elaborate the details of the various
mechanical systems. Verification is the process of checking at
each stage whether the output conforms to requirements for
that stage. For example: does the air conditioning system
deliver the specified cooling capacity to each room? Is the roof
rated to withstand so many newtons per square meter of wind
loading? Is a fire alarm located within 50 meters of each
location in the building?

Discussion – Validation – Building Design Analogy
At the same time, the architect has to keep in mind
the broader question of whether the results are
consistent with the ultimate user requirements.
Does the air conditioning system keep the
occupants comfortable throughout the building? Will
the roof withstand weather extremes expected at
the building site? Can the fire alarm be heard
throughout the building? Those broader concerns
are the essence of validation.

Discussion - Verification
In the initial stages of design, verification is a key quality assurance
technique. As the design effort progresses, verification activities
become progressively more comprehensive. For example, heat or
cooling delivery can be calculated and verified by the air conditioning
designer, but the resultant air temperature can only be estimated.
Occupant comfort is a function not only of delivered air temperature,
but also humidity, heat radiation to or from nearby thermal masses,
heat gain or loss through adjacent windows, etc. During the latter
design phases, the interaction of these complex factors may be
considered during verification of the design.

Discussion - Validation
Validation follows successful verification, and ensures that
each requirement for a particular use is fulfilled. Validation of
user needs is possible only after the building is built. The air
conditioning and fire alarm performance may be validated by
testing and inspection, while the strength of the roof will
probably be validated by some sort of analysis linked to
building codes which are accepted as meeting the needs of the
user-subject to possible confirmation during a subsequent
severe storm.

Design Verification
Verification activities are conducted at all stages and levels of
device design.
The basis of verification is a three-pronged approach involving
tests, inspections and analyses. Any approach which
establishes conformance with a design input requirement is an
acceptable means of verifying the design with respect to that
requirement.
In many cases, a variety of approaches are possible.

Design Verification
Complex designs require more and different types of
verification activities. The nature of verification activities
varies according to the type of design output. The
manufacturer should select and apply appropriate verification
techniques based on the generally accepted practices for the
technologies employed in their products. Many of these
practices are an integral part of the development process, and
are routinely performed by developers. The objective of
design controls is to ensure adequate oversight by making
verification activities explicit and measuring the thoroughness
of their execution.

Verification Testing Examples
Following are a few examples of verification methods and activities:
• Comparative tests with a proven design (side-by-side)
• Inspection of attributes
• Analytical Testing
• Failure modes and effects analysis.
• Package integrity tests.
• Biocompatibility testing of materials.
• Bio-burden testing of products to be sterilized.
• Functional Tests after Sterilization
For some technologies, verification methods may be highly standardized. In other cases,
the manufacturer may choose from a variety of applicable methods. In a few cases, the
manufacturer must be creative in devising ways to verify a particular aspect of a design.

Production Testing
Some manufacturers erroneously equate production testing with verification.
Whereas verification testing establishes conformance of design output with
design input, the aim of production testing is to determine whether the unit
under test has been correctly manufactured. In other words, production
testing is designed to efficiently screen out manufacturing process errors and
perhaps also to detect infant mortality failures. Typically, a small subset of
functional and performance tests accomplish this objective with a high degree
of accuracy. Therefore, production testing is rarely, if ever, comprehensive
enough to verify the design. For example, a leakage test may be used during
production to ensure that a hermetically-sealed enclosure was properly
assembled. However, the leakage test may not be sensitive enough to detect
long-term diffusion of gas through the packaging material. Permeability of the
packaging material is an intrinsic property of the material rather than an
assembly issue, and would likely be verified using a more specialized test
than is used during production.

Documenting the Verification Activities
Many verification activities are simply some sort of structured
assessment of the design output relative to the design input. When
this is the case, manufacturers may document completion of
verification activities by linking these activities with the signoff
procedures for documents.
This may be accomplished by establishing a procedure whereby each
design output document(e.g. forms) must be verified and signed by
designated persons. The presence of the reviewers' signatures on the
document signifies that the design output has been verified in
accordance with the signoff procedure.
Where do sampling plans come from? How are they developed?
Why would you want to revise a sampling plan?

Discussion
Whereas verification is a detailed examination of aspects of a design
at various stages in the development, design validation is a
cumulative summation of all efforts to assure that the design will
conform with user needs and intended use(s), given expected
variations in components, materials, manufacturing processes, and
the use environment.
When in the Design Process...Objective Evidence?
Design Verification
Design Validation
Machine Qualification
Process Validation
Calibration

SOP...Initial vs. Equivalent...Intended Use...DHF
Each manufacturer shall establish and maintain procedures for
validating the device design. Design validation shall be
performed under defined operating conditions on initial
production units, lots, or batches, or their equivalents.
Design validation shall ensure that devices conform to
defined user needs and intended uses and shall include
testing of production units under actual or simulated use
conditions.
Design validation shall include software validation and risk
analysis, where appropriate. The results of the design
validation, including identification of the design, method(s),
the date, and the individual(s) performing the validation,
shall be documented in the DHF.

Discussion
VALIDATION PLANNING
Planning for validation should begin early in the design process. The
performance characteristics that are to be assessed should be
identified, and validation methods and acceptance criteria
should be established.
For complex designs, a schedule of validation activities and
organizational or individual responsibilities will facilitate maintaining
control over the process. The validation plan should be reviewed for
appropriateness, completeness, and to ensure that user needs and
intended uses are addressed.

Discussion
VALIDATION REVIEW
Validation may expose deficiencies in the original assumptions
concerning user needs and intended uses. A formal review
process should be used to resolve any such deficiencies. As
with verification, the perception of a deficiency might be
judged insignificant or erroneous, or a corrective action
may be required.

Discussion
VALIDATION METHODS
Many medical devices do not require clinical trials. However, all
devices require clinical evaluation and should be tested in the actual
or simulated use environment as a part of validation. This testing
should involve devices which are manufactured using the same
methods and procedures expected to be used for ongoing production.
While testing is always a part of validation, additional validation
methods are often used in conjunction with testing, including
analysis and inspection methods, compilation of relevant scientific
literature, provision of historical evidence that similar designs and/or
materials are clinically safe, and full clinical investigations or clinical
trials.

Calibrated Equipment...QMS...Accountability
Verification and validation should be done with test equipment
calibrated and controlled according to quality system
requirements. Otherwise, there is limited confidence in the
data.

Protocol Driven...Document Control...Authorization
Verification and validation should also be done according to a
written protocol(s). The protocol(s) should include defined
conditions for the testing. The protocol(s) should be
approved before being used. Test protocol(s) are not
perfect for a design, particularly a new design. Therefore,
the designers and other verification personnel carefully
annotate any ongoing changes to a protocol. Likewise, the
verification personnel should record technical comments
about any deviations or other events that occurred during
the testing. The slightest problem should not be ignored.
During design reviews, the comments, notes and deviations
may be as important as test data from the formal
protocol(s).

Medical Devices used for Validation
Some manufacturers have historically used their best
assembly workers or skilled lab technicians to fabricate test
articles, but this practice can obscure problems in the
manufacturing process. It may be beneficial to ask the best
workers to evaluate and critique the manufacturing process by
trying it out, but pilot production should simulate as closely as
possible the actual manufacturing conditions.

Design Validation
Validation should also address product packaging and labeling.
These components of the design may have significant human
factors implications, and may affect product performance in
unexpected ways. For example, packaging materials have
been known to cause electrostatic discharge (ESD) failures in
electronic devices. If the unit under test is delivered to the
test site in the test engineer's briefcase, the packaging
problem may not become evident until after release to
market.

Validation - Environmental Conditions
Validation should include simulation of the expected
environmental conditions, such as temperature, humidity,
shock and vibration, corrosive atmospheres, etc. For some
classes of device, the environmental stresses encountered
during shipment and installation far exceed those encountered
during actual use, and should be addressed during validation.

Validation – Customers / Users / Patients ??
Particular care should be taken to distinguish among
customers, users, and patients to ensure that validation
addresses the needs of all relevant parties. For a consumer
device, the customer, user, and patient may all be the same
person. At the other extreme, the person who buys the device
may be different from the person who routinely uses it on
patients in a clinical setting. Hospital administrators,
biomedical engineers, health insurance underwriters,
physicians, nurses, medical technicians, and patients have
distinct and sometimes competing needs with respect to a
device design.

Documentation – Validation
VALIDATION DOCUMENTATION.
Validation is a compilation of the results of all validation activities.
For a complex design, the detailed results may be contained in a
variety of separate documents and summarized in a validation
report. Supporting information should be explicitly referenced in the
validation report and either included as an appendix or available in
the design history file.

Substantive Evidence to support labeling and claims
During verification, the complete device is exercised
such that all labeling, displays, and outputs are
generated, reviewed, and the results
documented. During the verification, all displayed
prompts and instructions are checked versus the
manufacturer's and FDA's labeling requirements
and versus the Instructions for Use (IFU).

Design Transfer
Preamble Page 52621, Comments #85→#87

Discussion – Transfer Foundations
Production specifications must ensure that manufactured devices are
repeatedly and reliably produced within product and process
capabilities. If a manufactured device deviates outside those
capabilities, performance may be compromised. Thus, the process of
encapsulating knowledge about the device into production
specifications is critical to device quality.
The level of detail necessary to accomplish this objective varies
widely, based on the type of device, the relationship between the
design and manufacturing organizations, and the knowledge,
experience, and skills of production workers. In some cases, devices
are produced by contract manufacturers who have no involvement in
the development and little or no contact with the designers. At the
other extreme, some devices are hand-crafted by skilled artisans
with extensive knowledge about the use of the product.

Manufacturing Considerations – Pilot Runs ??
Particular care should be taken when the product involves new and
unproved manufacturing processes, or established processes which
are new to the manufacturer. It may not be possible to determine
the adequacy of full-scale manufacturing on the basis of successfully
building prototypes or models in a laboratory and testing these
prototypes or models. The engineering feasibility and production
feasibility may be different because the equipment, tools, personnel,
operating procedures, supervision and motivation could be different
when a manufacturer scales up for routine production.

Transfer – Discussion – Design Review
No design team can anticipate all factors bearing on the success of the design, but
procedures for design transfer should address at least the following basic elements.
- First, the design and development procedures should include a qualitative assessment
of the completeness and adequacy of the manufacturing specifications.
- Second, the procedures should ensure that all documents and articles which constitute
the production specifications are reviewed and approved.
- Third, the procedures should ensure that only approved specifications are used to
manufacture production devices.
The first item on this list may be addressed during design transfer. The second and third
elements are among the basic principles of document control. As long as the production
specifications are traditional paper documents, there is ample information available to
guide manufacturers in implementing suitable procedures.

Production Specifications - Discussion
Historically, shortcomings in the production specifications tend to be
manifested late in the product life cycle. When the design is new,
there is often intensive interaction between the design and
production teams, providing ample opportunity for undocumented
information flow.
Later, as production experience is gained, some decoupling often
occurs between design and production teams. In addition, key
personnel may leave, and their replacements may lack comparable
training, experience, or institutional knowledge.
How do you prevent this decoupling?

Transfer of the Device...Sections...
Full Device...Process Specifications
The design controls require that each manufacturer
shall establish and maintain procedures to
ensure:
- That the device design is correctly translated into production
specifications
- It is common practice for sections of a design to be
transferred before the entire design is completed. The
QS regulation does not prevent such split or multiple
transfers
- Transfer is to be performed only for completed elements of the
design -- multiple transfers may not be used to bypass any
design, labeling or other GMP requirements

During successful Output...DMR...What is included?
A significant part of the transfer requirement is met when the
design output is being created. That is, some of the design
output documents are part of the DMR and are used
directly for production.
The remaining DMR documents are based on design output
information. A procedure is needed to cover the generation
of the remaining device master record documents based on
information in the design output documents.

Transfer...successful Verification...Change
Control...Transfer
Design transfer should assure that the section of the design
being transferred:
- meets input requirements;
- contains acceptance criteria, where needed;
contains design parameters which have been appropriately
• verified;
- is complete and approved for use;
- is fully documented in the DMR or contains sufficient design
• output information to support the generation of remaining
DMR documents; and
- is placed under change control if not already done.

Transfer over “the line”...manufacturability...resources
Design transfer may include training of production, installation
and service employees and such training should be covered
by or referenced by the transfer procedure.
You can transfer certain components and processes
throughout the design process

Design History File (DHF)
Preamble Page 52622, Comments #90 - 92

Definitions
820.30(j) Design history file.
■Each manufacturer shall establish and maintain a DHF for
each type of device.
■The DHF shall contain or reference the records necessary to
demonstrate that the design was developed in accordance
with the approved design plan and the requirements of this
part.
820.3(e) Design history file (DHF) means a compilation of
records which describes the design history of a finished
device.

DHF...start early...basis for DMR
The DHF covers the design activities used to develop the device,
accessories, major components, labeling, packaging and production
processes.
Name ten documents that could go into the DHF
Name five records that could go into the DHF
Documentation is what?________

Discussion
Virtually every section of the design control
requirements specifies information which should be
recorded. The compilation of these records is
sometimes referred to as the design history file.

A Tool for Investigations
...the manufacturer lacked design information necessary to
validate a design and maintain it throughout the product life
cycle.
This occurs for the most innocent of reasons-contracts expire,
companies reorganize, employees move on to new projects or
new jobs. Even when the designer is available, he or she may
forget why a particular decision was made years, months, or
even weeks before. Since design decisions often directly affect
the well-being of device users and patients, it is to the
manufacturer's benefit to maintain the knowledge base which
forms a basis for the product design and further investigation.

...and what about laboratory notebooks?
As an example of the level of detail which may be entailed, some
manufacturers have policies covering laboratory notebooks. Manufacturers
typically find that without such written procedures, a breakdown in
communications eventually occurs, resulting in a loss of control. These
procedures might address the following points:
• Laboratory notebooks are the property of the manufacturer,
not the individual.
• A separate notebook is to be maintained for each project, and
surrendered to the engineering librarian at the conclusion of the
engineer's active participation in the project.
• Laboratory notebooks are to be surrendered if the employee
leaves the company.
• Product development supervisors shall review employees' laboratory
notebooks at specified intervals to ensure that records are complete,
accurate and legible.

Location and Organization of the DHF
There are no requirements on the location or organization of
the design history file. In some cases, especially for simple
designs, the designer will assemble and maintain the entire
design history file.
For larger projects, a document control system will likely be
established for design documents, and these files will likely be
maintained in some central location, usually within the
product development department or centralized files
(electronic and/or hard copy).

...where is the DHF Located?
Except for small projects, it is unusual for all design history
documents to be filed in a single location.
The intent is simply that manufacturers have access to the
information when it is needed.
The manufacturer should establish procedures for multiple filing
systems which together satisfy that intent, there is no need to create
additional procedures or records.
Where do you keep your DHF(s)? DMR(s)? DHR(s)?

DHF...for each device type...
The design controls in 820.30(j) require that each
manufacturer shall establish and maintain a DHF for
each type of device.
Each type of device means a device or family of devices that
are manufactured according to one DMR. That is, if the
variations in the family of devices are simple enough that
they can be handled by minor variations on the drawings,
then only one DMR exists. Iterations…

Audit Strategy for DHF vs. Design Plan...Planning in
terms of 820.30
The QS regulation also requires that the DHF shall contain or
reference the records necessary to demonstrate that the
design was developed in accordance with the approved
design plan and the requirements of this part.
As noted, this requirement cannot be met unless the
manufacturer develops and maintains plans that meet
the design control requirements.

Design Review...DHF...Verification Discussions
The plans and subsequent updates should be part of the DHF.
In addition, the QS regulation specifically requires that:
the results of a design review, including identification of the
design, the date, and the individual(s) performing the
review, shall be documented in the DHF
design verification shall confirm that the design output meets
the design input requirements. The results of the design
verification, including identification of the design,
method(s), the date, and the individual(s) performing the
verification, shall be documented in the DHF.

DHF Content (examples)
Typical documents that may be in, or referenced in, a DHF are listed below:
-design plans;
-design review meeting information;
-sketches;
-drawings;
-procedures;
-photos;
-engineering notebooks;
-component qualification information;
-biocompatibility (verification) protocols and data;
-design review notes;
-verification protocols and data for evaluating prototypes;
-validation protocols and data for initial finished devices;
-contractor / consultants information;
-parts of design output/DMR documents that show plans were followed; and
-parts of design output/DMR documents that show specifications were met.

Plans were created...followed...specifications met
The DHF contains documents such as the design
plans and input requirements, preliminary input
specs, validation data and preliminary versions of
key DMR documents. These are needed to show
that plans were created, followed and
specifications were met.

DHF Value...investigation...change control...
re-design...living document...DMR Support
Value of the DHF
When problems occur during redesign and for new designs,
the DHF has the "institutional" memory of previous design
activities. The DHF also contains valuable verification and
validation protocols that are not in DMR.
This information may be very valuable in helping to solve a
problem; pointing to the correct direction to solve a
problem; or, most important, preventing the manufacturer
from repeating an already tried and found-to-be-useless
design.

Protect the Contents of the DHF
Based on the structure (or lack thereof) of the product development
organization, more or less extensive controls will be required. For
example, company policy should state unequivocally that all design
history documentation is the property of the manufacturer, not the
employee or contractor. Design and development contracts should
explicitly specify the manufacturer's right to design information and
establish standards for the form and content of design
documentation.

MidWest Process Innovation, LLC
Thank you
John Gagliardi
t
513-315-9820

Design Controls: Building Objective Evidence and Process Architecture to Meet FDA and ISO Compliance - OMTEC 2018

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Design Controls: Building Objective Evidence and Process Architecture to Meet FDA and ISO Compliance - OMTEC 2018