HFE is an essential and integral part of the inhaler device development process. The process requirements are primarily based on the core principles of safety and effectiveness. The HFE processes for the FDA and EU submissions are largely harmonized, but there are some minor differences. It is important that manufacturers of inhaler devices understand the process clearly so that they can comply with the requirements. Following the HFE process does not only fulfil the regulatory requirements but also helps you to develop better products. This presentation provides the holistic view of the HFE process in a simple schematic way, however every project is different and the process should be tailored accordingly.

1. 6 December 2016
RDD Asia 2016
Satisfying US and EU Human Factors Requirements
for Inhaler Devices
RDD Asia 2016
08-10 November
Suresh Gupta PhD (Cantab)

2. 6 December 2016 2
The Human Factors Engineering (HFE) process described in
the presentation is based on our extensive experience in this
area and our informed interpretation of the HFE guidance and
standards

3. 6 December 2016 3
About Cambridge Consultants
 We are an end-to-end product development
company with a strong emphasis on human
factors engineering (HFE).
 For over 55 years we have led the way in the
Cambridge hi-tech cluster for innovative design &
development.
 Our team of ~700 human factors engineers,
designers, engineers and scientists have an
enviable track record of world firsts and
breakthrough developments.
 Human factors engineering (HFE) is an integral
part of our Medical Development Process (MDP).
 Our MDP is compliant to ISO 13485 and US CFR
Title 21.

4. 6 December 2016 4
NEW DELHI
TOKYO
SINGAPORE
CAMBRIDGE
BOSTON
SAN
FRANCISCO
SEATLE
We have Global Presence

5. 6 December 2016 5
We have many years of experience working for pharma and medtech clients
Some examples

6. 6 December 2016 6
We have a long track record of successful inhaler device development
Some examples of respiratory devices
Conix
High performance
dry powder inhaler
Technology
licensed to 3M in
2008
Tobi ® podhaler
Inhaler for CF
Launched 2012
Design award
winner
T-Haler
Metered Dose
Inhaler compliance
& training device
Starhaler
60-dose dry
powder inhaler
Launched in India
NEXThaler
Breath actuated
inhaler with
mechanical dose
counter
Launched 2013

7. 6 December 2016 7
Satisfying US and EU Human Factors Requirements for Inhaler Devices
 Background
 HFE regulations and their focus
 HFE Process
– Fundamentals of HFE process
– FDA process
– EU (International) process
– Single process for both US and EU
 Conclusion

8. 6 December 2016 8
Definition of HFE
“Human Factors Engineering (HFE)
is the application of knowledge about
human behaviour, abilities, limitations,
and other characteristics of users to
the design of medical devices and
combination products”

9. 6 December 2016 9
Benefit of HFE
“The application of HFE helps
manufacturers to develop products
that
 reduce use errors,
 enhance patient and user
safety,
 improve product usability and
efficiency, and
 enhance user satisfaction”

10. 6 December 2016 10
HFE uptake
“The uptake of HFE in product
development has been slow because:
 traditional product developers have
often considered HFE only as a
desirable aspect of the development
process, or
 did not know how to incorporate it
into the process so as to realize its
benefit.”

11. 6 December 2016 11
Paradigm change
“The paradigm has started to
change
 with the introduction of HFE/UE
standards and guidance, and
 their enforcement by regulatory
bodies such as the FDA”

12. 6 December 2016 12
China
CFDA
Introduction
“HFE has become an
important discipline
for manufacturers
around the world”

13. 6 December 2016 13
Understanding HFE
“There are Standards and
Guidance specifying the HFE
process but they are not user
friendly!”
“This presentation attempts to
provide an overview of the HFE
process in a simple schematic
way, clarifying the US and EU
requirements and their differences.”

14. 6 December 2016 14
HFE Regulations and their Focus

15. 6 December 2016 15
HFE Standards and Guidance
 FDA Guidance (2016): Applying human factors and usability engineering to medical devices.
Guidance for Industry and Food and Drug Administration Staff.
 FDA Draft Guidance (2016): Human factors studies and related clinical study considerations in
combination product design and development. Draft Guidance for Industry and FDA Staff.
 FDA Draft Guidance (2016): List of highest priority devices for human factors review. Guidance for Industry
and Food and Drug Administration Staff.
 IEC 62366-1:2015: Application of usability engineering to medical devices.
 IEC/TR 62366-2:2016: Guidance on the application of usability engineering to medical devices.
 MHRA Draft Guidance (2016): Human factors and usability engineering. guidance for medical devices
including drug-device combination products.
 ANSI/AAMI HE75:2009: Human factors engineering – design of medical devices.
 IEC 60601-1-6:2010: Medical electrical equipment – Part 1-6: General requirements for basic safety and
essential performance. Collateral standard: Usability.
 ISO 14971:2007: Medical devices – application of risk management to medical devices.

16. 6 December 2016 16
FDA Guidance (medical devices)
FDA Guidance (2016): Applying human
factors and usability engineering to
medical devices. Guidance for Industry
and Food and Drug Administration Staff.

17. 6 December 2016 17
FDA Guidance (combination products)
FDA Draft Guidance (2016): Human
factors studies and related clinical study
considerations in combination product
design and development. Draft
Guidance for Industry and FDA Staff.

18. 6 December 2016 18
IEC 62366-1:2015 (medical devices and combination products)
IEC 62366-1:2015: Application of
usability engineering to medical devices.

19. 6 December 2016 19
ISO 14971
ISO 14971:2007/2012: Medical devices
– application of risk management to
medical devices

20. 6 December 2016 20
Medical Device, Combination Products and HFE Pathway
What Type
of Product?
MEDICAL DEVICE
MEDICINAL PRODUCT
Compliance with
Relevant Directive:
98/79/EC,
90/385/EEC,
93/42/EEC
Compliance
Assessed by NB
HFE Requirements
in IEC 62366-1
EU
Compliance
with Relevant
Parts of the
CFR Title 21
Part 200-499,
600-680
Compliance
Assessed by
CDER/CBER
US
Device and
Medicine
Device
Only
Medicine
Only
What is the
Principle
Mode of
Action?
What Type
of Medicine?
What Type
of Device?
In-Vitro Diagnostic
Active Implant
(Other)
Medical Device
Biologics
Drug
Compliance with
Relevant Parts of
CFR Title 21 Part
800-898
Compliance
Assessed by
CDRH for device
HFE
Requirements in
FDA HF Guidance
US
Compliance
with Medicinal
Products
Directive
2001/83/EC
Compliance
Assessed by
EMA
EU
Medicinal Product
(Combination Product)
Medical Device
(Ancillary Medicinal
Substance)
Device
Element
Medicinal
Element

21. 6 December 2016 21
Focus of HFE Process
Freedom from unacceptable riskSafety
Safety
Resources expended in relation
to effectiveness
Efficiency
User Satisfaction Freedom from discomfort and
positive attitude towards product
Other Commercial
Benefits
For example, improved sales
If any of these
affects safety or
effectiveness, then it
is the focus of
HFE/UE process
Superior Usability
(usability beyond safety
and effectiveness)
Generally NOT
the focus of
HFE/UE
Regulatory
Process
Effectiveness Accuracy and completeness
Focus of
HFE/UE
Regulatory
Process
Usability related to safety and effectiveness

22. 6 December 2016 22
Benefits of HFE Process
Improved sales
Effective product
Competitive advantage
Reduced time to market
Simpler training
Reduced demand for
customer support
Better treatment
compliance rates
Better application of
currently available
technology
Increased utilization of
available features
Fewer returned products
Reduced chances of
product recall
Reduced chances of
litigation
Safe product

23. 6 December 2016 23
Human Factors Engineering Process

24. 6 December 2016 24
Fundamentals of HFE process
Understand Users and Use Characteristics
Patients, Users, Use-Environment, Operating Principles, etc.
− Contextual enquiry
− Observation
− Interviews
− Desk-based research
Analyse Safety and Effectiveness Issues
What could go wrong in terms of safety and effectiveness
− Task/functional analysis
− Investigating known use-related problems
− Use-related risk assessment
Validate
Demonstrate that the product is safe and effective
− Simulated use testing
− Actual use testing
Evaluate Residual Risk
Analyse whether residual risks are acceptable and/or outweighed by the benefits
− Risk management
− Risk-benefit analysis
HFE/UE Report
Summarize all HF activities concluding safety and effectiveness
− HFE/UE Report
Design, Evaluate and Optimize
Design
Optimize Evaluate
− Design of user-interface
− Heuristic analysis
− Expert review
− Cognitive walk-through
− Simulated use assessment

25. 6 December 2016 25
FDA Human Factors Process
Understanding Users, Uses and Use-Environments
Identification and Categorization of Critical Tasks
Based on Severity of Harm
Use-Related
Risk
Assessment
(e.g. use FMEA)
Investigation into Known
Use-Problems
Analytical Analyses and Evaluations
Empirical Analyses and Evaluations
- Contextual Inquiry
- Interviews
- Formative Evaluations (cognitive walk-through,
simulated use testing)
- Task Analysis
- Heuristic Analysis
- Expert Review
Design and Optimization
of User Interface
Device (controls, display, etc.),
Packaging, Labels, IFU, Training
Materials, etc.
Develop and Implement
Risk Mitigation/Control
Measures
- Inherent Safety by Design
- Protective Measures
- Information for Safety
Risk
Management
Process
Risk Management Preliminary Analyses and Evaluations Design of User Interface
Critical Tasks to be Included in Validation Testing
Optimised User Interface
Representative of Final Design
Evaluate
Residual Risk Validation Testing
HFE/UE Report
Summarising HFE Activities Leading to Safe and Effective Product

26. 6 December 2016 26
If a New Problem is
Identified
If Further
Improvement is
Practicable and
Necessary
EU Human Factors Process
Use Specification
User Interface Characteristics
Related to Safety
- Task analysis
- Functional analysis
- Investigation into known
use problems
Risk
Management
Process
Risk Management
Design and Optimization
of User Interface
Develop and Implement
Risk Mitigation/Control
Measures
Design of User Interface
Hazard-Related Use Scenarios for Summative
Evaluation
Optimised User Interface
Representative of Final Design
Evaluate
Residual Risk Summative Evaluation
Usability Engineering File
Results and Record of Usability Engineering Process / Activities
Use-Related
Risk
Assessment
(e.g. use FMEA)
Hazard and
Hazardous
Situations
Hazard and
Sequence of
Events Leading
to Hazardous
Situations
User Interface
Evaluation Plan
Design of User
InterferenceHazard-Related Use Scenarios
Based on Severity of Harm
Formative Evaluation
- Cognitive Walk-Through
- Expert Review
- Usability Test
User Interface
Specification

27. 6 December 2016 27
Common Approach to Satisfy both US and EU Submissions
HFE/UE Report (Usability Engineering File)
Use Specification / Statement of Intended Use
Understanding Indication, Patients, User, Use-Environment, Operating Principles, etc.
User Interface Characteristics Related to Safety/
Analytical Analyses and Evaluations
Identification of Known Use-Related Problems
Task Analysis
Formative Evaluation(s)
It is an iterative process and may require more than one formative evaluations
Good HF/UE practice suggests conducting at least one formative evaluation
ahead of a summative evaluation (validation testing)
Summative Evaluation / Validation Testing
With representative users, use-environment and final design
Summarising all HF activities
Concluding the product is safe and effective
DESIGNANDDEVELOPMENTPROCESS
OtherAspectsofDesignandDevelopmente.g.Engineering
UserInterface
Finalisation
UserInterface
Development
UserInterface
Improvement
OtherRiskAssessments,e.g.DesignandProcessRiskAssessments
RISKMANAGEMENTPROCESS
Use-RelatedRisk
AssessmentFinalisation
InitialUser-Related
RiskAssessment
Use-relatedRisk
AssessmentUpdate

28. 6 December 2016 28
Example of a Legacy
Product (Product
with UOUP)
Tailored HFE Processes
 There are situations where full-scale human factors or
usability engineering process may not be required
– Legacy products (products with user-interface
of unknown provenance, UOUP)
– Generic / biosimilar products
– Products for use in a clinical trial
– Products with low risks
– Products with partial or no HFE documentation
(Remediation Work)
Use Specification
(IEC62366-1:2015, Annex C, C.2.1)
Post-production Information
(IEC62366-1:2015, Annex C, C.2.2)
Hazards and Hazardous Situations related to
Usability (Risk Analysis)
(IEC62366-1:2015, Annex C, C.2.3)
Risk Control
(IEC62366-1:2015, Annex C, C.2.4)
Residual Risk Evaluation
(IEC62366-1:2015, Annex C, C.2.5)
Use-related
Risk
Assessment
Risk Evaluation
(ISO 14971:2007 Section 5)
Overall Residual Risk Acceptability
(ISO 14971:2007 Section 7)
Risk
Management
Report
HFE Conclusion Report

29. 6 December 2016 29
Conclusions

30. 6 December 2016 30
Conclusions
 HFE is an essential and integral part of the inhaler device development process.
 The process requirements are primarily based on the core principles of safety and
effectiveness.
 The HFE processes for the FDA and EU submissions are largely harmonized, but
there are some minor differences.
 It is important that manufacturers of inhaler devices understand the process
clearly so that they can comply with the requirements.
 Following the HFE process does not only fulfil the regulatory requirements but
also helps you to develop better products.
 This presentation provides the holistic view of the HFE process in a simple
schematic way, however every project is different and the process should be tailored
accordingly.

31. 6 December 2016
Cambridge UK
Registered No. 1036296 England
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in Innovation. www.Altran.com
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