Managing the Marriage: Device Development in a Pharmaceutical Environment

www.team-consulting.com© Team Consulting 2010

Managing the Marriage:Device Development in a Pharmaceutical Environment

Chris Hurlstone, Team Consulting Ltd.

3rd Pre-filled Syringe Conference

London, October 2010

Pre-Filled Syringes, 2010, slide 2www.team-consulting.com© Team Consulting 2010

Marrying Drugs and Devices - what’s the problem?

• Drug discovery: Dozens of scientists working year after year with the most sophisticated technology imaginable

• Drug manufacture: Trillions of atoms being marshalled into amazingly complex molecules by the most careful, delicate manufacturing processes

• Now all you need to do is just get the stuff into a person. Surely that’s the easy part... Isn’t it?


Drug development vs. Device development – a few clear differences…

• Development processes

• Regulatory constraints

• Production processes

• User issues

• The Culture!


Drug development & Device development – conflicting requirements

Can’t goto market with anunsafe product

Need to be right first time

but… Need to get

to market asquickly as possible

Drug pipelinescan be uncertain

Need to be flexible for aslong as possible

but… Need to work ina rigid regulatory

framework

For a successful ‘marriage’ these conflicts need to be resolved…… and that requires focus on some key aspects of device development


Paths to a successful marriage….

1. Plan your joint development

2. Understand important requirements

3. Consider the individual

4. Manage risk throughout


Pilot manufacture / DVT

Pilot manufacture / DVTDetailed DesignDetailed DesignProof of PrincipleProof of Principle IndustrialisationIndustrialisationOpportunity

DefinitionOpportunity

Definition Concept DesignConcept Design

• User Requirements

Specification • Design / technology

research• Interaction design• Concept generation

and work-shopping• Visualisation• Evaluation• IP investigation• Design review• Structured selection• Product Requirements

Specification

• Visualisation• User Interface• Instructions• 3D CAD detailing• Cost analysis• Design Review• Engineering Analysis

• FEA• Tolerance

analysis• DFMA

• Prototyping• Testing• User trials• Software verification• Beta electronics

• Concept development• Proof of principle rigs• Test protocols and

planning• Proof of principle testing• Top level user studies• Engineering analysis• Initial DFMA• Mathematical modelling• Simulations• Alpha electronics• Software development• PRS update

• Assessment of user

requirements and

technical constraints• Feasibility research• Performance

characterisation• Life Cycle

Management• Direction setting

investigation• Decision support• Generation of Market

Requirements

Specification / Design

Brief

1 2 3 4 5

Lead concept(s) selected

POP testing complete Detailed design complete & frozen for

tooling

Pilot Design Verification Complete

and approved

Design & processes signed-off & approved for launchMajor Milestones

• Tooling procurement• Testing / evaluation• Component

reconciliation• Tool correction &

modification• Process development• Assembly & test jigs

and fixtures• DV plans & protocols• Design verification• User studies & pre-

clinical trials• QC development &

documentation• Design review

• Production tooling

design, build and

validation• Production DVT• CAD database

updates• Clinical Trials support• Manufacturing

support• Assembly and test

equipment • Process validation

and qualification• Knowledge &

technology transfer

Risk management

Programme Plan Risk Management Plan

Product Risk AssessmentSystem Risk Assessment

User Risk Assessment Risk assessment & mitigation iterationsProcess Risk Assessment

Regulatory

Design Development Plan, Regulatory Strategy, Essential Requirements, Technical/Design History File, Clinical Input

Device Development Documentation

0

Planning…


Planning is NOT just about Gantt charts

• Design and Development Plan

• Risk Management Plan

• Human Factors Engineering Plan

• Design Verification Plan

• Validation Plan

• As a checklist:

– Study FDA 21 CFR 820.30 and ISO 13485:2003

– Think about your DHF & Technical File content


Planning: everybody has their favourite do’s and don’ts

Combining drug and device development plans efficiently will require flexibility, contingency and some work at risk. Only burn bridges when you have to!


Understanding Requirements – Device Specifications

URSPRS

Design Specs


Specifications - The waterfall diagram

UserNeeds

Design Input

DesignProcess

DesignOutput

MedicalDevice

DesignVerification

DesignValidation

Review

URS

PRS

Design Specs

We need to think in particular about how key requirements can differ for similar devices


Cartridge-based Injectors (multi or single dose)

Pre-filled Syringe-based Injectors (single dose, not multi-dose)

Rel

oad

able

(R

eusa

ble

)D

ispo

sable

Flexpen (NN)

Preotact(Ypsomed)

Autopen(OM)

NovoPen 4 (NN)

EasyPOD (Merck Serono)

SymlinPen (Ypsomed)

RediPen (BD)

DUAL CHAMBER CARTRIDGE PEN

(for lyophilised drugs)

Penlet (Haselmeier)

(not on market)

SimpleJect(OM)

SureClick (SHL)

Humira pen (OM)

Epipen (Meridian)

Humalog Pen (EL)

EpiCard (Intelliject)

Autoject II (OM) Snapdragon (OM)

Leva (B&O)BD auto-injector


Reusable Disposable

Single dose Multi dose

IM SC

Regular Unpredictable / emergency

Frequent Infrequent

Self injection Third party injection

Home Portable

Fixed dose Variable dose

Manual needle insertion Auto needle insertion

Manual delivery Auto delivery

Specifications – drugs and devices….

Growth hormone

Migraine


Specifications – key technology elements

Some elements of device technology are strongly influenced by drug properties (e.g. stability, viscosity), so can only be confirmed when the formulation is fixed

Needle Sterility

Dose Control

Depth Control

Power Source

Safety Interlocks

Trigger Mechanisms

Delivery Indication

Needle Safety

Reset Mechanisms

Primary Drug Packaging

Others are primarily driven by the needs of the user. You probably know who they are... but do you know what they will do?!


The User…

… is a primary source of risk

… is unpredictable

… needs worrying about from Day 1.

Usability is very hard to change at the last minute!


Combine analytical and empirical approaches

EmpiricalAnalytical


Human Factors Engineering to HE75

Full Spectrum of User Research

Human Factors Engineering on device developments

Opportunity Definition

Phase

Uncover Unexpressed User Needs

Ethnographic Research

Market Research

CoreEmpiricalMethod

CoreAnalytical

Method

Main image from AAMI HE75:2009


HFE: making what is safe, not what is ‘nice’

For medical devices, being right first time is

an imperative


Manage Risk Throughout

Risk Management

is like gravity.

Not just a good

idea - it’s the law.

Flowchart from ISO 14971:2009


The Risk Management Plan

• Defines responsibilities for risk management

• Defines the scope

• Defines risk assessment and mitigation tools and processes

• Defines the severity of generic hazards, and other risk rating guidelines

• Ensures the risk assessment process is sufficiently independent of the design process

• Conforms to ISO 14971:2009


Manage Risk Throughout

• Risk Management for devices needs to consider a range of perspectives– The ‘User’ or ‘Application’– The ‘Product’ or Design’– The Manufacturing Process & Supply Chain

• Different techniques are appropriate at different stages, including– Hazard Analysis– Fault Tree Analysis– FMEA/FMECA

• Risk mitigation is a critical part of design verification and validation, but should be starting much sooner


In summary

The right plan

The right specifications

User focus

Managed risk

Flexibility in a rigid environment

Managing cultural differences

Minimising compromise

The right first time imperative

For a well managed marriage… and hopefully a happy one!


For further information, please contact

Chris Hurlstone

Tel: +44 (0)1799 532 741

Email: [email protected]

mailto:[email protected]

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Managing the Marriage: Device Development in a Pharmaceutical Environment