Parenteral Drug Delivery in the Future: A View of Developments, Implications and Opportunities

PDA: A Global

Association

Parenteral Drug Delivery in the

Future:

A View of Developments,

Implications and Opportunities

Andy Fry Founder, Team Consulting Ltd 8th November 2011

• The parenteral delivery device

• HFE, Compliance and usability – what„s the connection?

• Mature optimisation– influential improvements

• Disruptive change - transforming technologies

• Implications for the future

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Parenteral Drug Delivery in the Future

• Tablets we can swallow – mostly

• Ointment we can rub on – usually

• For virtually all other prescription medications :

‘The delivery device is the drug to patient interface’

(Georg Rößling, February 2011)

3

The Parenteral Delivery Device

• Some fundamental points arise when we consider the device this way;

– No device, no therapy

– Bad device = Bad therapy

– Bad drug = Bad therapy

• The right device is as important as the right drug

4

„the drug to patient interface‟


• HFE, Compliance and Usability – what„s the connection?

• Mature optimisation– influential improvements



5


Compliance – some research data

50%

estimated

compliance

across chronic

illnesses &

lifestyle changes1

measured

compliance

with oral

medications for

Type 2 diabetes2

53%

to

67% 30%

to

35%

compliance

with oral

methotrexate for

RA3

compliance with

inflximab infusion

for RA4

41% 52%

compliance with

adalimumab

autoinjector for

RA4

25%

to

35%

compliance with

daily oral

bisphosphonate

for osteoporosis5

35%

to

45%

compliance with

weekly oral

bisphosphonate

for osteoporosis5

change

delivery

route

reduce

dose

freq

side

effects

1 - Haynes et al (1979) Compliance in health care. Johns Hopkins University Press, 1979

2 - Paes et al (1997) Impact of dosage frequency on patient compliance. Diabetes Care 20:1512 -1517

3 - Viller et al (1999) Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J

Rheumatol 10: 2114-22

4 - Hetland et (2010) Arthritis & Rheumatism 62: 22–32

5 - Cramer et al (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis.

Osteoporos Int 18:1023–103

Compliance – influencing factors co

mp

lian

ce

chronic

conditions younger age /

male gender

poor

education

disability

driving wilful non-compliance

treatment

cost

side effects

poor perceived

treatment

effectiveness/

understanding

of disease

lack of social /

professional

support

relationships

lack of

confidence/

perceived

ability to take

medication

dosing

regime

complexity

forgetting

driving unintentional non-compliance

What can device developers influence?

• what can‟t we change? – the disease condition

– the drug: side effects, symptomatic relief

– the patient‟s age / gender / disabilities / socioeconomic status

• what can we influence? – the formulation: e.g. dosing frequency

– the delivery route: e.g. from IV to SC, depot implants, wearable devices/patches

– the demands on the user associated with dose delivery

– the support provided to the patient to help them adhere to dosing regime

– the patient‟s perceptions of and attitudes to their treatment

co

mp

liance

chronic

conditionsyounger age /

male gender

poor

education

disabilityco

mp

liance

co

mp

liance

chronic


male gender

poor

education

disability

chronic

conditions

chronic


male gender

younger age /

male gender

poor

education

poor

education

disabilitydisability

treatment

cost

treatment

cost

side effectsside effects

poor perceived

treatment

effectiveness/

understanding

of disease

poor perceived

treatment

effectiveness/

understanding

of disease

lack of social /

professional

support

relationships

lack of

confidence/

perceived

ability to take

medication

dosing

regime

complexity

forgetting

demands on user

support of user

Mature Optimisation; Improve Compliance through

Usability - Reduce Demands on Users

Minimise the core physical and cognitive burden of delivering therapy

• Target - eliminate the negatives

– perfect device reliability / consistency of performance in hands of users

– no significant use-related risks

– accommodate full range of user input • grip styles, operation styles

• maximise ease of use

– minimise delivery pain / anxiety

• But there are some conflicts

– clarity of feedback vs. discretion/privacy

– some users want to be in „control‟, others want „distance‟

• Excellent usability = zero “delivery task” burden …

…. but usability alone cannot address the “self-management task” burden (i.e. we have to accept that total compliance can never be achieved)

9

?

Disruptive Change; Improve Compliance through

Additional Functionality – Support Users

Reduce the cognitive and emotional burden of managing treatment. Opportunities include :

• Wearable / implantable devices

• New formulation enabled by new device

– reduced dosing frequency

– reduced dose size

– reduced dose discomfort

• On-board electronic features

– reminders

– dose logging / memory

• Links to other devices

– smartphone self-management apps

– diagnostic devices – theranostics

• Links to social networks

– e.g. www.patientslikeme.com/

10

HFE, Usability, Compliance and Regulation

• Follow usability engineering / human factors

process with passion and creativity

– FDA guidance

– ISO/IEC 62366 (incl. ANSI/AAMI HE74)

– ANSI/AAMI HE75:2009

• This is not a ‘Nice to have’ but a regulatory

necessity

• Reduce risk and improve compliance

Design

Control

Activities

Contextual

Inquiry

Literature

Reviews

Complaints

Analysis

Market

Research

Task Analysis

User Profiles

Use Environment

Heuristic Review

Risk Analysis

Usability

Objectives

Prototyping /

Simulations

Iterative Design

Formative

Usability

Testing

Risk Analysis

Cognitive

Walkthroughs

Expert

Reviews

Cognitive

Walkthroughs

Summative

Usability

Testing

Risk Analysis

Production

Units (or

Equivalent)

Summative

Usability

Testing

Field Studies

Concept

Phase

Design

Input

Design

OutputVerification Validation

Perform

Studies &

Analysis

Design

Requirements

Design

Specifications

Test Output

Against Input

Test Against

User Needs

Human

Factors

Activities

• Three essential attributes for success;

– Usability The patient must be able to use the device without difficulty or errors

– Functionality The device must address needs and function reliably and consistently

– Manufacturability The device must be manufacturable at acceptable cost

• All three attributes must be in balance

– Get the first two right to satisfy the regulators and benefit the patients

– Get the last one right to satisfy prescribers and payers (and get it to the patient)

• Dominance of one attribute at the expense of others may spoil

an otherwise good device

• Failure to hit the mark in any one area is usually terminal for the device

(and possibly the therapy concerned)

HFE as part of a balanced process

• The Parenteral Delivery Device

• HFE, Compliance and Usability – what„s the connection?

• Mature optimisation – Influential improvements



13


Mature optimisation;

„Established‟ product types – Autoinjectors

• A new generation of autoinjectors is

emerging

• Different manufacturers, different designs but

some fundamental objectives in common;

– consistent and reliable

– designed for manufacture

– competitively priced

– compact in size

– wide applicability for a range of therapies

– simple and intuitive in use

14

• BD Hypak™ has a long and admirable pedigree

– But not originally designed for autoinjector use

– Integration of formed glass with precision mechanisms is challenging,

demanding tighter tolerances

• BD continue to develop the Hypak™ family

– BD Physiolis™ syringe

• Current product

– BD Hypak™ for Biotech

• New specification for autoinjector compatibility

– BD Neopak™ - in development

• 6σ quality vision, new production process

15


Next generation glass pre-filled syringes

Images by kind permission of BD Medical – Pharmaceutical Systems

COC / COP cyclic polyolefin syringes

• Injection moulded, designed to replace glass

– Much tighter dimensional control than glass

– Reduced need for siliconisation

– No tungsten issues

– Robust; greater safety, no breakage losses

• In many ways a very promising design alternative

• Several leading producers already offering prefilled syringes

– West, BD, Schott, Gerresheimer and others

• Some resistance to adoption

– For drug product approved in glass, time and cost to change material

– Lower oxygen barrier than type 1 Borosilicate glass

• In Japan, 65% of all syringes are COC/COP and have been for several years

West Daikyo Crystal Zenith


Alternatives to glass as a syringe material

Image by kind permission of West Pharmaceutical Services

17


Improved Syringe Siliconisation Control

Good syringe Bad syringe

Images by kind permission of ZebraSci

• silicone-free lubrication system for

syringe-barrels, plungers and needles

• Perfluoropolyether (PFPE) chemistry – atmospheric plasma crosslinking process immobilises PFPE

lubricant onto the device surface

• Glass and plastic (COC, COP, PP) cartridges

and syringes (Luer and staked needle)

• FDA 510(k) approval for use in piston syringe

applications received in 2007

• Multiple benefits – Low break-free force

– Low, uniform extrusion force

– Minimal protein aggregation

– Low friction coating on needles

18


Improved Syringe Lubrication

Images by kind permission of TriboGlide


• Compliance and usability – what„s the connection?

• Mature optimisation – influential improvements



19


EEDDs are already becoming established - examples

• easypod® for delivery of HGH – simple in use (attach needle, position against skin, press button)

– device keeps track of daily therapy

– preset dosing

– GUI

• OmniPod ® system for delivery of insulin – wearable insulin pump („pod‟)

– wireless management unit („PDM‟)

– integrated glucose meter

– downloads to health management system

• Both products – reduce demands on the user associated with dose delivery

– provide support to help patient comply with dosing regime

– respond to the particular needs of the patient groups concerned

• The number of EEDDs applications is growing

Disruptive Change; EEDDs

(Electronically Enabled Delivery Devices)

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easypod® image by kind permission of Merck Serono

OmniPod ® images by kind permission of Ypsomed

Disruptive Change; EEDDs - Opportunities

• Potential for improved compliance through reduced

cognitive, physical and emotional burden – Reminders for infrequent therapies

– Prompts to aid correct use

– Rewards e.g. for children

– Fully automated, invisible needle

– Usage trends / history

– Complex functions simplified e.g. titration

• Sophisticated interface will not suit all user groups – One size won‟t fit all

– Just because functions are possible they aren‟t necessarily desirable

21

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Disruptive Change;

Wearable devices SmartDose ® image by kind permission of West Pharmaceutical Services

SteadyMed ® image by kind permission of SteadyMed Therapeutics, Inc

• Increasing range of : – Names – patch pumps, infusers, bolus delivery devices

– Technologies – electromechanical, spring driven, elastomeric

– Devices – from an increasing number of established and emerging

organisations

• Common theme – SQ delivery of high viscosity and/or high volume meds

– e.g. biopharm/macromolecules

• Up to 10 ml in 60 mins typical with no / minimal pain

• Convenient – adhere to skin, then automated sequence;

– insert needle / cannula, deliver dose, disable, then remove / dispose

• Suited to chronic therapy where dose size, viscosity

or both preclude autoinjector delivery

Disruptive Change;

Novel delivery technologies

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• Needle-free („jet„) injection

• No sharps hazard, no needle phobia

• Delivery <100msec; no issue of „hold„ time

• Small molecule delivery well established

• Sumavel® DoseproTM for migraine since Q1 2010

• Needle-free delivery is unaffected by viscosity

• same injection time from 1cP to 3000cP

• Delivery of macromolecules without denaturation

• MAb„s, proteins, vaccines

Delivery technology enables formulation opportunities

to be realised

Images by kind permission of Zogenix Inc.

• Xeris; ultra-low volume, ready-to-use bio-pharmaceuticals

• Non-aqueous paste – no reconstitution

• Suited to peptides, proteins, antibodies and small molecules

• No cold chain, stable as pre-mixed paste or liquid at room temperature

• Ultra-low injected volume hence very low discomfort

• Ideal for self-administration

Formulation opportunity enabled via the right delivery technology

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Disruptive Change;

Novel formulations

Images by kind permission of Xeris Pharmaceuticals, Inc

Aqueous Non- Aqueous Aqueous Non- Aqueous


• Compliance and usability – what„s the connection?

• Mature optimisation – influential improvements



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Implications for the future

• The delivery device is the drug to patient interface

– Devices will remain a fundamental part of parenteral product offering

• HFE ensures that user issues are given appropriate weight

– Regulators will assess usability, user should benefit from improved compliance

• Plenty of scope to improve current technologies further

– Products, materials and processes

• Emerging technologies are presenting new opportunities

– Delivery technology and formulation enablers

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Acknowledgements

Many thanks for images, data and permissions granted by;

• BD Medical – Pharmaceutical Systems

• Merck Serono S.A.

• Oval Medical Ltd

• Owen Mumford Ltd

• SHL Group AB

• SteadyMed Therapeutics, Inc.

• TriboGlide, Inc.

• West Pharmaceutical Services, Inc.

• Xeris Pharmaceuticals, Inc.

• Ypsomed AG

• ZebraSci, Inc.

• Zogenix, Inc.

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Thank you

Andy Fry

Founder

Email: [email protected]

Tel: +44 1799 532739

Mob: +44 7764 178439

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Parenteral Drug Delivery in the Future: A View of Developments, Implications and Opportunities

Health & Medicine

Transcript of Parenteral Drug Delivery in the Future: A View of Developments, Implications and Opportunities