Automating

a compliant approach to fast, innovative product development

John AvellanetCerulean Associates LLC

www.CeruleanLLC.com

© Cerulean Associates LLC all rights reserved

Acknowledgements

Tim Ulatowski

Dan O’Leary

Anita Fauchier

Mike Weber

Nancy Singer

Karen Steinberg

Kerry McCarter

Akos Bartha

Carl Anderson

Jackie Cassada

John Lincoln

Jim Shore

Tom Colonna

Terry Winchell

Chris Szustkiewicz

Kim Trautman

Larry Nicholson

Jan Welch

David Elder

Annamarie Kempic

Doug Throckmorton

Jonathan Lee

2

Agenda

core requirements

industry challenges

an ideal solution

beyond compliance

next steps

This is not legal advice. Information in this presentation draws upon a variety of sources, including published FDA warning letters, personal experiences, interviews and research, all or any of which may or may not have been prepared or conducted by Cerulean Associates LLC. Cerulean Associates

LLC does not provide a warranty concerning the accuracy of the information contained in this presentation. The contents of this presentation are intended for general information only and should not be construed as legal advice. Cerulean Associates LLC assumes no liability for actions taken or not taken as a

result of the information in this presentation. This presentation is copyrighted 2011 by Cerulean Associates LLC, all rights reserved.

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Understanding Requirements

governmental regulations

core documentation and reporting

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21 CFR 820.30

(a) “General. (1) Each manufacturer…shall establish and maintain

procedures to control the design of the device in order to ensure that

specified design requirements are met.”

Translation for FDA inspectors“The purpose of the design control subsystem is to

control the design process to assure that devices meet

user needs, intended uses, and specified requirements:

• Inputs must be documented

• Outputs must be documented

• Confirm that device outputs are traceable to design inputs”

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21 CFR 803.18

(b) (1) (i) “…including all documentation of your deliberations and

decisionmaking processes used to determine if a device-related death,

serious injury, or malfunction was or was not reportable….”

Translation for FDA investigators“A firm must demonstrate that it exercised “good faith” in

any attempts to obtain required data…. In addition, the

Center believes that the parameters of good faith must,

at a minimum, comport with the level of risk/nature of

the device….”

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21 CFR 806.20

(b) (4) “Justification for not reporting the correction or removal action to

the FDA, which shall contain conclusions and any followups….”

Translation for FDA investigators“Verify that non-reported device corrections or removals

meet the following criteria based on design controls:

• Risk is not increased

• Repairs are not unexpected

• Part replacement is not earlier than expected”

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Other Requirements

FDA Guidance Documents• Human Factors Points to Consider for IDE Devices (1996)

• Human Factors Implications of the New GMP Rule: Overall Requirements of the New Quality System Regulations (1997)

• Design Control Guidance for Medical Device Manufacturers (1997)

• Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk Management (2000)

• Guidance for Industry 21 CFR Part 11; Electronic Records; Electronic Signatures Validation (2001)

• General Principles of Software Validation (2002)

• Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (2005)

• Draft Guidance for Industry and Food and Drug Administration Staff - In Vitro Companion Diagnostic Devices (2011)

• Draft Guidance for Industry and Food and Drug Administration Staff - Mobile Medical Applications (2011)

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Other Requirements

GHTF Guidelines• SG3 N:99 Quality Management Systems - Process Validation

Guidance (2004)

• SG3 N:15 Implementation of Risk Management Principles and Activities Within a Quality Management System (2005)

• SG1 N:11 Summary Technical Documentation for Demonstrating Conformity to the Essential Principles of Safety and Performance of Medical Devices (STED) (2008)

• SG4 N:28 Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers - Part 1: General Requirements (2008)

• SG1 N:068 Essential Principles of Safety and Performance of Medical Devices (2011 draft)

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Industry Challenges

information overload

tracking and documenting

change is inevitable

disconnect between groups

innovate with VOC

getting to market faster

outdated technology

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Information Overload

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Source:

FDA Acronyms & Abbreviations List

(FDA.gov, 2011)

FDAISO

IEC

IEEE ANSI

GHTF

Funny Horror Story

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“We submitted a 510(k) with the FDA. A few months later, we got a 482.

They checked our SOP, SRD, URS, DHF, and VMP then issued us a

483. The FDA said we didn’t have good V&V processes and we need to

improve our CAPA, FMEA, and RVTM documentation and processes.

So now our management team feels SOL and they have to ask for

more VC to get FDA approval.”

Translation

“This fictitious play on acronyms company was using

outdated and manual efforts to update documents,

versus using a tool that helps automate, trace and

document for them….”

Tracking and Documenting

Development Must Track and Document• SOP : Standard Operating Procedure for Design Control

• DHF : Design History File

• SRD : System Requirements Document or PRD

• URS : User Requirements Specifications or SRS

• CAPA : Corrective and Preventative Action

• RVTM : Requirement Verification/Validation Trace Matrix

• VMP : Validation Master Plan

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Change is Inevitable

Requirements Early Design Protype Production Clinical Final Production

Perception

Reality

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Source:

Adapted from Scott Ambler, Agile Modeling (2002)

Time (development cycle)

Co

st

of

Ch

an

ge

(in

cl.

do

cu

me

nta

tio

n, tr

ackin

g, ve

rify

ing

ea

rlie

r

tests

, a

dd

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sts

, e

tc.)

Disconnect Between Groups

Lack of Effective Communication• Change : Usually Delayed and Not Automated

• Handoffs : Usually Delayed and Not Automated

• Vernacular : Usually Different Naming and Taxonomy

• Departmental Silos : Disparate Processes and Systems

Nobody Looking at Bigger Picture• Decisions : Made at Departmental Level

• Traceability : Usually Not Accurate or Automated

• Documentation : Requires Multiple Data Elements

• Perception : Already have Solution; QMS, PLM, etc…

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Innovate with VoC

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Get VoC and Use It

• Get it early and often

• Share it on use cases/user stories

• Manage and communicate feedback from clinicals

Don’t let Documentation Hold You Back

• Lower risk items can be fast-tracked

• Agile: Scrum, XP

• Six Sigma: LEAN

Getting to Market

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Source:

Design Control Guidance For Medical Device

Manufacturers (2011, FDA)

Getting to Market Faster

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Source:

Get to Market Now! Turn FDA Compliance

into a Competitive Edge (2010, Logos Press)

AUTOMATE

Outdated Technology

Challenges from Evolving• Reactive Mode : Too Much Manual Operations

• Departmental Silos : Disparate Systems

• Fear : Resistance to Change and Validation

• Compliance : Over Interpretation of Regulations

• Too Big : Simply Believe It Cannot Be Solved

• Knowledge : Simply Don’t Know Technology

• Cost : Perception of Total Cost

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An Ideal Solution

traceable content reuse

integrated into daily activities

transparent enforceable workflow

processes generate good documents

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Beyond Compliance

greater visibility

better content reuse

focus on getting work done

faster development cycles

stronger user adoption

higher quality

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Next Steps

document ideal solution

get management buy-in

find right solution

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Want More?

Seapine Life Science Solutionshttp://www.seapine.com/lifesciences.html

FDA Expectations for Traceabilityhttp://www.youtube.com/v/iB8JDuHTdIk

Six Exercises to Strengthen Traceability

http://downloads.seapine.com/pub/papers/SixExercisesStrengthenTraceability.pdf

Traceability Resourceshttp://www.seapine.com/traceability.html

The Seapine View Bloghttp://blogs.seapine.com

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Picture Credits

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Photos, images and clip art that appear on these slides have been used to enhance this presentation and may NOT

be used for commercial or promotional purposes without permission from copyright holders. Do not remove or copy

from this presentation.

Contact:

iStockphoto.com

Microsoft Corporation

Seapine Software

Cerulean Associates LLC

Logos Press