Device Change Management For Inhaled Products: Loy Britto, Ph.D. Glaxosmithkline

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Device Change

Management for
Inhaled Products
Loy Britto, Ph.D.
GlaxoSmithKline
ISAM Congress Munich 2015
Topics to be covered

 Update on ISO/TC 084/WG 15: Device Change Management


 Guidelines for development of drug products- Quality by Design (QbD) (ICH 8,
9 and 10)
 Combination products – Inhaled products are a combination of a medical device
and medicine
 Focus on Metered Dose Inhaler(MDI) products – Post approval changes
 Quality attributes of MDI products
 Impact of device changes on product attributes and management of these
changes through aspects of a QbD approach
 Examples
 Introduction of a dose counter
 Changes to MDI canister internal coating
 MDI valve design
 Indirect device impact (changes to formulations, analytical methods, processes,
complaints, inspections. Recalls, OOS results)

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Device Change Management
Post Approval Changes – Application of QbD principles

 Product development occurred before or after implementation of QbD


principles
 Control strategy is in place
 Control of input materials
 In-process controls
 Controls around container closure systems
 Controls around analytical methods
 FMEAs conducted
 Risk assessments have been conducted
 Regular review of trending, control charts, process capability etc.
 Device changes – change management process
 Need to revisit elements of the control strategy
 Understand impact from a FMEA perspective. Perform a product risk assessment.
 Manage changes proactively

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Device Change Management
Schematic Diagram of a Metered Dose Inhaler

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Device Change Management
Quality Attributes of a Metered Dose Inhaler Product

Quality Attributes Critical Quality Attributes

 Appearance and Color  Particle size distribution, fine


 Water or Moisture content particle dose
 Dehydrated alcohol content  Dose content uniformity through
container life
 Microscopic evaluation
 Content uniformity of dose
 Spray pattern
 Identification
 Plume geometry
 Microbial limits
 Valve delivery – Shot weight
 Foreign particulate matter
 Weight of canister contents
 Leachables
 Drug content in a canister
 Impurities and degradation
 Leak Rate
products

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Device Change Management
Interactive Nature of Inhaled Drug Products

Components

Inhaled
Formulation Drug Methods
Product

Processes

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Device Change Management
Example: Dose Counters and Dose Indicators in MDIs

Location
 Around the nozzle block of
the actuator
 On top of the can
 Counters and Indicators

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Device Change Management
Impact of addition of dose counter or dose indicator

Air flow Addition of Impact on


Changes to changes
a Dose automated
device
counter or analytical
deposition
Dose methods
indicator (DTU &CI)

 Ex-Device dose
 Throat Impact on
deposition  Patient  Material filling
 Delivered dose Handling changes
 Changes in
process
Studies  Electrostatics
deposition on  Valve  Extractables
CI stages function
 Overages  Counter
robustness

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Device Change Management
Example: Change in can coating formulation

 Change in solvent used in the coating formulation.


 Driven by environmental, health, safety concerns
 May need to consider a change in polymers used in the coating
material
 Impact on:
 Control strategy
 Coating process
 Coating quality – conformity and pinholes
 Extractables and leachables
 Drug deposition on can wall
 Overages
 Delivered dose and Cascade impaction results

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Device Change Management
Cross-Sectional view of a Metered Dose Inhaler Valve
(Courtesy Aptar Pharma)

Upper Stem

Body

2nd Stem Gasket


Metering Chamber

Ferrule Neck Gasket

1st Stem Gasket


Ring

Lower Stem

Spring

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Device Change Management
Complexity of MDI Valve and its Assembly Process
(Courtesy Aptar Pharma)

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Device Change Management
Impact of change in valve design

 Valve design changes can be driven by a multiplicity of factors


 Problems that arise due to propellant leakage
 Valve function issues
 Change in valve seal properties
 Shot weight changes
 Change in materials – shrinkage, extractables, dimensional controls
 Impact on product critical and quality attributes and critical process parameters
 Changes in delivered dose and Cascade impaction results
 Changes in leak rate
 Changes in valve frictional behaviour
 Analysis and management of valve design changes
 Optimization of crimp parameters
 Addition of lubricants to the valve
 Changes in valve dimensions
 Assessment of valve functionality

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Device Change Management
Conclusions

 Inhaled products are a very complex dosage form


 Device changes occur all the time and many of them are mandatory
 Impact of device related changes can be significant
 Change management entails the use of a structured FMEA and Risk
analysis based approach
 Device changes can alter existing control strategy
 Changes are very time consuming, labor intensive and require
regulatory submissions of various types
 In the pharmaceutical industry we have transitioned and implemented
good Quality Management Systems.
 ISO standards for “Device change management” are not expected to
alter to any significant extent the currently existing quality control
measures

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Device Change Management
Thank you

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