Considering The Patient Interface - IPAC-RS The Patient Interface . ... – In response to user...

Considering The Patient Interface Dave Parkins

IPAC-RS/UF Orlando Inhalation Conference

Overview

2 18 March 2014 IPAC-RS/UF Inhalation Conference

• Why do we have to consider device similarity/equivalence

• Role of in-vitro methods

• The patient interface

• Considering the relevant patient population

• Role of Risk Management – Case example – Considerations in applying risk assessments

Diversity of device designs


Differences can be either visible or invisible to the patient

Why do we need to consider device equivalence ?


• We have to consider the impact of device/product changes throughout the whole product lifecycle

– In response to user feedback during device design

e.g http://www.ukpharmsci.org/2012resourcepack/PDFPresentations/WCS1_1410_Stephen_Eason.pdf

– Feedback during clinical studies – Results of robustness testing – To permit industrialisation – Feedback from patients, healthcare professionals in market – Manufacturing process improvements – New suppliers – supply security – Enforced changes in supply chain – Innovator / generic equivalence

http://www.ukpharmsci.org/2012resourcepack/PDFPresentations/WCS1_1410_Stephen_Eason.pdf

Critical Factors for Patient Safety & Efficacy


Patient Safety & Efficacy

Formulation Patient Interface

Device

In-vitro methods


• In-vitro methods & tests provide important data to assess impact of change

Performance / Characterisation – Aerodynamic Particle Size Distribution – Dose Uniformity – Actuation Force – Air Flow resistance – Plume Geometry Robustness – Drop Testing – Transport Testing

Need to be aware of limitations of the in-vitro test ?

Cascade testing is a Quality Control Test

Test conducted under fixed conditions

Difference in deposition mechanisms

In-vitro - deposition is by impaction

in- vivo – deposition by impaction, sedimentation & diffusion.

Methodology has been adapted by various groups – Alberta Idealised Throat

Finlay et al, Respiratory Drug Delivery 2010 185 – 193

– Elung Burnell et al, Resp. Med. 2001, 95, 324-330

– Mixing Inlet Olsson et al. J. Aerosol Med. Pulm. Drug Delivery 2013 , 26(6), 355-368

Does not take into account the patient interface

Examples of differences with potential to impact patient interface


• Inhalation Manoeuvre co-ordination – Need to be aware of changes impacting MDI plume velocity, duration &

temperature • Plume velocities range 150ms-500ms Gabrio et al, Int J Pharm. 1999, 186, 3-12

• Changes in mouth feel – cold freon effect. – DPI emitted dose times & can vary Haugney et al , Resp. Med. 2010, 104, 1237-1245

– Perception of dose from powder loading (Higham et al. Br J.Clin.Pharmacol. 1995, 40, 281-282

– Change in AFR of DPI – impacts inspiratory effort

• Ergonomic change – Change in handling method – Change in patient feedback – audible, visual

Examples of differences with potential to impact patient interface


• Mouthpiece Geometry change – Changes in Mouthpiece geometry can influence throat deposition Coates et al Pharm.Res. 2007, 24(8), 1450-1456

– Changes can be particle size dependant

% D

epos

ition

Effi

cien

cy

Flow rate L/min

Impact of mouthpiece diameter on deposition efficiency

After Lin et al, J Aerosol Med. 2001, 14(3), 335-341

Mouthpiece diameter

8um

4um

2um

How Patients use our products


• Patients ability to use their own product – Error rates for patients using their own products

• MDI 74.6%, Three DPIs 6.8 – 43.2% Khassawneh et al. Resp. Care 2008, 53(3), 324-328

• MDI 24%, Three DPIs 17 - 24% • Melani et al. Ann. Allergy Asthma Immunol. 2004, 93(4), 439-446

• Role of Education in patients ability to use their own Product % of Patients with critical errors for

a range of DPIs on first & second use Adapted from Schulte et al. J. Aerosol Med.Pulm. Drug Del.

2008 21(4) 321-328

Device

%


Frequency of handling errors for 4 DPIs stratified by severity of airway obstruction

Impact of Age & Disease State on Patient Handling

Frequency of handling errors for 4 DPIs stratified by patient age

Schematics adapted from Wieshammer et al , Respiration 2008,75,18-25

% %

ICH Q9 Principles of quality risk management


Two primary principles of quality risk management are:

• The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; and

• The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk

Device Difference vs Risk


Increasing risk of device difference impacting product equivalence

Increasing device similarity

Device designs different

Cosmetic change

n-2 change to plastic

supplier of non-critical component

After PQRI Workshop report, Demonstrating Bioequivalence of locally acting OIPs. J.Aerosol Med. Pulm. Drug Delivery 2010, 23(1), 1-29

Mouthpiece Design Case Study


• Design changed from an established shape

• Initial design selection supported by in-vitro assessment

• Team also undertook an early Patient Handling Study using prototype models to establish acceptability of the mouthpiece shape to patients

• Study undertaken early to enable design freeze of mouthpiece shape prior to pivotal clinical studies.

Mouthpiece shape attached to block for early PHS

Mouthpiece Design Case Study


• Proposed design tested in the early Patient Handling Study indicated shape was not well received by patients due to fit and feel in mouth

• Patient feedback accepted, thus decision made to improve outer shape, whilst maintaining internal geometry

• Drug Product Critical Quality Attributes potentially impacted • Aerodynamic Particle Size Distribution • Considered a low risk based on design knowledge

• Improved design well received in follow-up Study – 86% stated it was an improvement

• Risk mitigated by incorporation into pivotal clinical studies

An Insight into current thinking


Work of the IPAC-RS Device Working Group, reproduced with permission. ISAM/IPAC-RS European workshop on equivalence considerations for orally inhaled products for local action. Oct 2010. Frankfurt

An Insight into current thinking


User Handling Study ~ 80%

Clinical efficacy~ 25%

Work of the IPAC-RS Device Working Group, reproduced with permission. ISAM/IPAC-RS European workshop on equivalence considerations for orally inhaled products for local action. Oct 2010. Frankfurt

Conclusion


• The need to understand the relevance of device changes applies across the product lifecycle

• Its important to understand the patient interface & relevant populations when evaluating a change

• Risk Management approaches can be used to identify appropriate studies

• There is little consensus on required studies, driven in part by significant diversity in product designs

Thank you

Considering The Patient Interface - IPAC-RS The Patient Interface . ... – In response to user...

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