fda design controls: what medical device makers need to know

The Complete Guide to FDA Design Controls

Part 1 & 2

April 26th, 2016

About the Presenter

David Amor is the co-‐founder and CEO

of Medgineering & QuickConsult.

• Adjunct Professor, St. Cloud State

University (SCSU) – MTQ628

Design Controls

• 9+ years of QA/RA consulting

including DHF / risk mgmt

remediation projects

• FDA & EU expert in QMS

@medgineering

[email protected]

786.546.1806

Medgineering is a medtech consulting firm

based in Minneapolis, MN focusing on

regulatory submissions and quality systems.

www.medgineering.com

www.21cfr820.com

Online medtech consulting marketplace – on

demand experts for Q&A and projects!

www.myquickconsult.com

About the Presenter

Jon Speer is the Founder & VP QA/RA

of greenlight.guru.

• 17+ years in medical device industry

• Product development engineer,

quality manager, regulatory

specialist

• 40+ products to market

• Expert at QMS implementations

• Dozens of ISO audits & FDA

inspections

@creoquality @greenlightguru

[email protected]

+1 317 960 4280

greenlight.guru produces beautifully simple

quality, design control and risk management

software exclusively for medical device

manufacturers. We help you bring higher

quality devices to market faster and with less

risk.

http://greenlight.guru

In Part 1, you'll learn about Intended Use, User Needs, Design Inputs, Design Reviews, Design History File (DHF) and Risk Management.Specifically:• The importance of getting your intended use right up front• The difference between a user need and a design input

that's verifiable• What stakeholders need to be involved in the process and

why• When and how many design reviews you should hold• Why FMEA alone is NOT risk management and how to

integrate risk into the design and development process

In Part 2, you'll learn about Design Outputs, Device Master Record (DMR), Design Verification and Validation (V&V), Design Transfer and Regulatory Submissions.Specifically:• Why your design outputs need to be more than a drawing

and their relationship to your DMR• How usability and human factors fits into the overall product

development• Making sure you build the correct device and build it

correctly with design V&V• Common mistakes people make during design transfer to

production and how to avoid them• When you can and should make your regulatory submission

Design ControlsAn introduction

21 CFR 820.30.

Design Controls – when?Any Class II or Class III medical device developed in the US – part of quality system (QMS).

Investigational Device Exemption (IDE) – 21 CFR 812.

User Needs & Design InputThe FDA differentiates between

user needs and technical requirements

Regulation Description21CFR 820 Quality System RegulationSubpart C Design Controls

Use a development plan. Keep it short and sweet. Don’t overcommit and don’t make it too prescriptive.

820.30 Design Controls Design Planning


The extent of design and development planning should reflect company size and complexity and any outsourcing.

• Refining is OK – especially for new portfolio products

• Identify key milestones and dates only• Detail should be dependent on risk• If outsourcing development work,

identify the resources and integration


“You state in your response that you plan on making your design plan more robust. We would like to clarify that this plan, as per 21 CFR 820.30(b), “shall identify and describe the interface between groups that provide, or result in, input to the design development process. The plans shall be reviewed, updated, and approved as design and development evolves.” The design plan for Avex CX2 and CXi2, reviewed during the current inspection, was observed to lack this data including, but not limited to, completed and approved plans for: Development, Clinical, Risk Management, Quality Processing, Manufacturing, and Manufacturing Qualification”

Discussion Point: Lack of documented planning shows poor oversight of your processes. Development planning may change with new information – up to the point of design freeze.


Design inputs need to be organized and differentiated between users, customers and stakeholders. Design inputs must be clear and verifiable.

820.30 Design Controls Design Inputs


Design requirements are the single most important factor in 820.30

“There’s never time to do it right but there’s always time to do it over!”• Comprehensive – per risk• Methodical• Linked to clinical or other rationale


“Drilling down” inputs is critical.

• Refining is OK – especially for new portfolio products

• Identify key milestones and dates only• Detail should be dependent on risk• If outsourcing development work,

identify the resources and integration



User Needs

Marketing Needs

Customer Needs

Other Stakeholder

Needs

“Concept” Documents per FDA Guidance 1997 Design Controls


Am I ever going to tell you that I need a catheter

with a tensile strength of 10 +/-‐ 2 N?


User Needs

Marketing Needs

Customer Needs

Other Stakeholder

Needs


Product Requirements

• Solution independent• Clear• Concise• Verifiable


User Needs

Marketing Needs

Customer Needs

Other Stakeholder

Needs



User Needs

Marketing Needs

Customer Needs

Other Stakeholder

Needs

Product Requirements Specifications

WHAT? HOW!


The catheter shall be easy to manipulate.

The catheter shall have a torque ratio

of 1:1

User Need(Requirement)

Design Input(Requirement)

Design Output(Specification)

Material specifications

Test methods

Drawings




of 1:1

This may involve iterative testing until the design input requirement is determined.• TBD in initial drafts of DI

documents are acceptable –help guide feasibility testing!

• May shift over time• Impact assessment


“Failure to establish and maintain adequate procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient, as required by 21 CFR 820.30(c)”

Discussion Point: When you create a user needs / requirement document, are you linking it back to the intended use of the device?


Design Inputs must be clear (unambiguous) and verifiable.

• If basing design inputs on a standard, make sure the standard reference is specific, clear, and test-‐able

• When you think of design inputs, think “engineering” and “getting technical”

• Find a resource for writing requirements



“Device shall be portable”….



“Device shall be compliant to ISO 10993-‐1…”



Device shall be flexibleDevice shall be formed into a 50 mm diameter coil and straightened out for a total of 50 times with no evidence of cracking or deformity.

NOTE: assess the level of granularity or detail based on requirement criticality/ risk.

VS


F P I S.

• Functional: what does the device do?• Performance: accuracy, conditions,

operational limits, reliability, etc.• Interface: what does the device need to have

to work with accessories or external items?• Safety: does the device need precautionary

measures or safety margins?

A note on drafting requirements.• Language is important

a) ‘Shall’ vs. ‘Should’a) “Must have” vs. “Nice to have”

b) Avoid “as applicable” or “as required” in final DI • Avoid contradicting requirements• System à sub-‐system

a) Particularly useful for contracting


A note on drafting requirements.• Avoid comparative requirements• Ex: “…shall be 20% better than the predicate.”

• Avoid multiple objectives in same requirement• Avoid “NOTEs”!!!• INCOSE “Writing technical requirements”



Don’t stress about documenting design inputs in proof of concept or feasibility phases. Be agile!

• FDA distinguishes between R&D and finished product – remember this!

• Design inputs apply to the commercial product (“how do I know the design is in control?”)

The importance of traceability.

“Failure to establish and maintain adequate procedures for verifying the device design, as required by 21 CFR 820.30(f). Specifically, design outputs were not always evaluated to demonstrate that the outputs met design inputs.”

Risk ManagementAn overview

Risk Management Design Controls

Intended Use is important for Design Controls & Risk Management.

Risk Management & Design Controls are about demonstrating a medical device is SAFE and EFFECTIVE.

Risk Management Design Controls

Product Risk Management is a cycle, even during product development.

• Start Risk Management process early• Use Risk Management process to

improve product design• Use Design Controls to support Risk

Controls / Mitigations

RISK MANAGEMENT -‐ systematic application of management policies, procedures, and practices to the tasks of analyzing, evaluating, controlling, and monitoring risk

RISK -‐ combination of the probability of occurrence of harm and the severity of that harm

ISO 14971 Risk Management Key Terms

HAZARD -‐ potential source of harm

HAZARDOUS SITUATION -‐ circumstance in which people, property, or the environment are exposed to one or more hazard(s)

HARM -‐ physical injury or damage to the health of people, or damage to property or the environment

SEVERITY -‐ measure of the possible consequences of a hazard


RISK ANALYSIS -‐ systematic use of available information to identify hazards and to estimate the riskRISK ESTIMATION -‐ process used to assign values to the probability of occurrence of harm and the severity of that harmRISK EVALUATION -‐ process of comparing the estimated risk against given risk criteria to determine the acceptability of the riskRISK ASSESSMENT -‐ overall process comprising a risk analysis and a risk evaluationRISK CONTROL -‐ process in which decisions are made and measures implemented by which risks are reduced to, or maintained within, specified levelsRESIDUAL RISK -‐ risk remaining after risk control measures have been taken


ISO 14971 Risk Management Process Overview

ISO 14971 Risk Management Establish Framework

ISO 14971 Risk Management Risk Analysis

ISO 14971 Risk Management Risk Analysis

I can be a valuable resource throughout the

Risk Management Process!

Include end-‐users as part of the process.

Hazards

Foreseeable Sequence of

Events

Hazardous Situations

Harms

ISO 14971 Risk Management Risk Evaluation

ISO 14971 Risk Management Risk Evaluation

Risk Evaluation criteria shall be established and should be specific to your product.

• Use sources like MAUDE and other industry databases.

• Consult with end-‐users to understand true severity.

• Evaluate other similar products.• Leverage standards and guidance

documents.

ISO 14971 Risk Management Risk Assessment

ISO 14971 Risk Management Risk Control


Risk Controls are means to demonstrate risks have been reduced to acceptable levels.

Priority of Risk Control options:1. Inherent safety by design2. Protective measures in the medical

device itself or in the manufacturing process.

3. Information for safety.Recommend identifying Risk Controls for ALL risks.


My Design Outputs, Design Verifications, and Design Validations can be used as Risk Control Measures.

ISO 14971 Risk Management Risk Acceptability

ISO 14971 Risk Management Risk Acceptability

Have me help you with risk / benefit analysis of your

product.

Medical benefits of the medical device need to outweigh the risks to patients and end-‐users.

ISO 14971 Risk Management Risk Management Report

ISO 14971 Risk Management Production / Post-‐Production

Design ReviewAn overview


Design reviews shall be planned and conducted at appropriate stages during medical device product development.

820.30 Design Controls Design Review


“Failure to document the design review results, including the date, in the design history file, as required by 21 CFR 820.30(e).”“Design reviews were not performed and/or documented for the . . .design project as required in the work instruction or the design plan.”“Design reviews were conducted; however, the records fail to indicate the date or dates the design reviews were conducted and fail to indicate the results of the design reviews as required in the work instruction.“However, there were no records of any design reviews having been conducted after the design changes were implemented or transferred to production.”


Timing of design reviews is a function of design planning. Frequency of design reviews should reflect complexity of product development.

• All design controls need to be part of design reviews.

• Design plan shall identify when design reviews are to happen.

• Design reviews shall include an “independent reviewer”.

• Design reviews shall include appropriate functions.

Design History FileWhat goes in DHF?


DHF contains documented evidence that medical device was developed according to established design plan.DHF contains all design controls.

820.30 Design Controls Design History File (DHF)


“Failure to establish and maintain a design history file for each type of device, as required by 21 CFR 820.30(j). For example, your firm was unable to demonstrate when key elements of a design history file for the design project were conducted and approved, such as design inputs, outputs, verification, validation, and design transfer.”


If it isn’t documented, then it didn’t happen. Document all Design Controls and keep records in an organized DHF.

• Establish a DHF per product.• Use Design Reviews to confirm Design

Controls have been documented. • Compile DHF into a “single source of

truth”.


It is my responsibility to document design controls and maintain

the DHF.

Q&A

Part 1

David Amor@medgineering

[email protected]

786.546.1806


www.21cfr820.com


Jon Speer@creoquality @greenlightguru

[email protected]

+1 317 960 4280

Quality Management Software

Exclusively for Med Devices


Getting in Touch

The Complete Guide to FDA Design Controls

Part 2

In Part 2, you'll learn about Design Outputs, Device Master Record (DMR), Design Verification and Validation (V&V), Design Transfer and Regulatory Submissions.Specifically:• Why your design outputs need to be more than a drawing

and their relationship to your DMR• How usability and human factors fits into the overall product

development• Making sure you build the correct device and build it

correctly with design V&V• Common mistakes people make during design transfer to

production and how to avoid them• When you can and should make your regulatory submission

Design Outputs & DMRDesign Outputs – more than just drawings!


Design outputs aren’t just specifications and drawings.

820.30 Design Controls Design Outputs


What can I show you in my books to demonstrate that the design inputs are being met/ fulfilled/ satisfied – how can I prove it?

• “Establish and maintain procedures for documenting design output in terms that allow an adequate evaluation of conformance to design input requirements”


• PLAIN ENGLISH: “We need a documented way to show how we show that our design inputs are met – a drawing, a specification, results of a test, methods, etc.”

• “Design output procedures shall contain or make reference to acceptance criteria….”


• PLAIN ENGLISH: How do we know a design input requirement is met? Acceptance criteria. The output must be clearly marked to be able to show this!

• “and shall ensure that those design outputs that are essential for the proper functioning of the device are identified.”


• PLAIN ENGLISH: ‘Essential for proper functioning’ means you should know the Intended Use and what design aspects are most critical to meet it.


Design outputs: format and type

Drawings Material Specification

Inspection reports.

Service instructions.

MfgInstructions

Batch Records

Testing instructions.

Software code.

QA specs/ procedures.

Packaging/ Labeling.

Risk MgmtFile Test results.


“Failure to establish and maintain adequate procedures for verifying the device design, as required by 21 CFR 820.30(f). Specifically, design outputs were not always evaluated to demonstrate that the outputs met design inputs.”

Discussion Point: Some companies use DOORS or other similar requirements traceability programs – what are the pros and cons with those programs?


”For example, change summary report, DP#05-‐11 – “ICL Change of Packaging Solution from (b)(4) to (b)(4)” lacks the necessary attachments, references and reports necessary to compare the design inputs with the design outputs and determine the adequacy of the verification.”

Discussion Point: Some companies use DOORS or other similar requirements traceability programs – what are the pros and cons with those programs?

The total finished design output consists of the device, its packaging and labeling, and the device master record.


The DMR is the “one stop shop” for design outputs, often maintained in a DMR Index.

Design Verification & Design Validation

An overview

820.30 Design Controls Design Verification

Did I design my medical device

correctly?


Design Output(Specification) Design Verification

820.30 Design Controls Design Validation

Did you design the correct medical

device?

User Needs Medical Device Design Validation


“Failure to establish and maintain adequate procedures for verifying the device design. Design verification shall confirm that the design output meets the design input requirements, as required by 21 CFR 820.30(f). For example:Your firm failed to validate test methods implemented during design verification testing. These test methods were created in-‐house to verify your firm’s design inputs; however, they were not based on and did not follow a national standard.Your firm failed to follow its test procedure during design verification testing.Your firm performed design verification prior to establishing design inputs.”


“Your firm failed to establish (i.e., define, document, and implement) and maintain design validation procedures to ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g).For example, your firm failed to implement its established procedure for design validation. . . However, prior to commercially releasing your product, your firm failed to conduct design validation of the device constituent part of this combination product, as required by your SOP. ”


Design Verification demonstrates that the medical device Design Outputs meet the Design Inputs.



Design Verification shall provide clear, objective evidence that Design Outputs meet Design Inputs

• Consider Design Verification when defining Design Inputs

• Establish a Design Verification Plan (and do so early)

• Define verification methods• Demonstrate acceptance criteria is met



of 1:1


Design Output(Specification)

Material specifications Plans

Drawings

Design Verification

Results

Methods


Testing

Inspection

Analysis

Design Verification Plan

Design Verification Methods


• Design Inputs must be clear (unambiguous) and verifiable.

• Design Outputs must be defined so that conformance to Design Inputs may be demonstrated.

• Need to establish “acceptance criteria”.• Establish (and validate) Design

Verification methods.


Testing

Inspection

Analysis

Design Verification Plan Results

Design Verification Methods


Did I design my medical device

correctly?


Design Output(Specification) Design Verification


Design Validation demonstrates that the medical device meets the needs of the end-‐user(s).



Design Validation shall provide clear, objective evidence that the medical device meets the needs of the end-‐users.

• Establish a Design Validation Plan (and do so early)

• Use regulatory product classification• Involves “clinical evaluation” in actual or

simulated use with actual end-‐users• Product is production equivalent • Includes the entire product, including

packaging and labeling


• “Clinical evaluation” does NOT just mean actual use.

• Actual use will likely require addressing additional regulatory criteria.

• For many devices, simulated use is more than sufficient.


User Needs Medical Device

Plans

Design Validation

Results

Methods

The catheter shall be easy to manipulate.


TESTING!!

Inspection

Analysis

Design Validation Plan

Design Validation Methods


• Design Inputs must be clear (unambiguous) and verifiable.

• Design Outputs must be defined so that conformance to Design Inputs may be demonstrated.

• Need to establish “acceptance criteria”.• Establish (and validate) Design

Verification methods.


TESTING!!

Inspection

Analysis

Design Validation Plan Results

Design Validation Methods


Did you design the correct medical

device?

User Needs Medical Device Design Validation

Design TransferNot an event – but a process!


Design transfer is the translation of all of the design work to the production and testing processes that will make it commercial-‐izable.

820.30 Design Controls Design Transfer

• Myth: Design Transfer is an event• Reality: Design Transfer is an iterative, continuous process

• Myth: Design Transfer is Operations’ responsibility• Reality: Design Transfer is a collaborative effort between all of the functions involved in design and development

• Myth: Design Transfer occurs after “design freeze”• Reality: Design Transfer begins early in design and development, and is part of design refinements (design changes) that lead to a “final” design. Design Transfer can not end until the DMR is finalized.

Design Transfer Myths820.30 Design Controls Design Transfer

Source of Misconceptions21 CFR Part 820.30 Design Control

b) Design & Development Planningc) Design Inputd) Design Outpute) Design Reviewf) Design Verificationg) Design Validationh) Design Transferi) Design Changes

Which gets visualized as:

Planning Design Input

Design Output

Design Review

Design Verification

Design Validation

Design Transfer

But the process really looks more like this:

Design & Development Planning

Design Input

Design Output

Design Verification

Design Validation

Design Transfer

Design Review


Design Transfer Completion• All Device Master Record (DMR) elements reviewed,

approved, and production released

• All (DMR) elements are managed under formal change control

• Risk assessments completed and all identified risks appropriately dispositioned

• Defined and implemented test strategy for incoming, in-‐process, and final acceptance testing

• Plans in place to monitor and/or control features identified as critical to quality

• Process validation complete

• Test methods validated and complete

• Inspection procedures, visual inspections, and workmanship standards are complete

• Installation and servicing procedures are complete

• All equipment identified and calibrated and maintenance procedures are in place

• Manufacturing personnel and inspectors have been trained

• All supplier agreements and qualifications are complete

• Procedures in place to ensure control of device handling, storage and distribution of product

• Procedures in place to ensure identification and traceability of product

• Design verification testing performed and demonstrates design outputs meet design inputs

• Design validation testing performed demonstrates design meets user needs & intended uses

• All elements of the Design Transfer Plan have been completed or otherwise addressed



Discussion Point: a process should identify what represents “accurate translation” of the device design.

“There is no assurance that a design transfer procedure has been adequately established for [PRODUCT] to […] ensure an accurate translation of the device design and conformance to predefined user needs and intended uses.

There is no assurance that design transfer procedures have been adequately established for each rework/reconfiguration process of Passport V Monitor to ensure an accurate translation of the device design.”

Regulatory SubmissionsThe DHF forms the basis for your objective evidence

that the device has been designed to besafe and effective

Who are the regulators?

United States

European Union

DOJ enforcement

US Device Classifications21 CFR 860

• Classified according to risk and “criticality” to patient/ end-‐user

• (3) letter code groupings with names and attributes

• Used to track adverse events and field actions

• As new classification product codes are created, a device may be re-‐assigned into a new product code.

• Guidance exists for identifying the scope and critical aspects of a product code.

Class I Class II Class IIInot intended to help

support or sustain life or be substantially important in preventing impairment to human health, and may not present an unreasonable risk of illness or injury

more critical than Class I but designed to perform as indicated without causing injury or harm to patient or

user.

support or sustain human life, are of substantial

importance in preventing impairment of human health, or present a

potential, unreasonable risk of illness or injury

LOW RISK MEDIUMRISK HIGH RISK

General Controls General Controls + Special Controls

510(k)

General Controls + Premarket Approval

(PMA)

General Controls

• Basic requirements for all medical device companies per MDA• Applies to all devices; Class I only has to follow general

controls (with some exceptions)• Includes provisions:

• Adulteration• Misbranding• Device registration and listing• Premarketing notification (exemptions in XXX.9s)• Banned devices• Notification – repair, replacement, refund• Records and reports• Restricted devices• GMPs (Quality System Regulation)-‐ some exemption

Class I Class II Class III

Why do I need to comply to ISO 13485?

Submitting a Medical Device in United States

General controls + 510(k) or PMA depending on risk and intended use of device

Implement a quality management system

21 CFR 820 (QSR)Registration & Submission

Pre-‐market notification

The 2 main pathways of getting to US market.

Pre-‐market approval (PMA)

The 510(k) – Substantial Equivalence

SubstantialEquivalence

Technological Characteristics

Intended Use= &

or

Different Technological Characteristics

No new safety or efficacy concerns

+

Pre-‐market notification

Traditional

Special (20%)

Abbreviated (5%)

510(k) Content (21 CFR 807.87)

• Admin paperwork (cover pages, statements• Device information: name, intended use, classification• Company information: location, certifications• Labeling • Substantial equivalence assessment

o Device specifications and reference applicable guidance documents, special controls, or standards; photographs or engineering drawings

o Testing datao Comparison charts

• Information on biocompatibility, sterilization, materials analysis, etc.

510(k) Data

http://www.emergogroup.com/resources/research/fda-‐510k-‐review-‐times-‐research

The SE Letter.

Q&A

Part 2

David Amor@medgineering

[email protected]

786.546.1806


www.21cfr820.com


Jon Speer@creoquality @greenlightguru

[email protected]

+1 317 960 4280

Quality Management Software

Exclusively for Med Devices


Getting in Touch

fda design controls: what medical device makers need to know

Health & Medicine