1. Director, Regulatory Affairs
Pan African Harmonization Working Party (PAHWP) – Technical Working group meeting and 3rd African Regulatory Forum on Medical Diagnostics – IVD Regulatory Framework
Benny Ons
Director, Regulatory Affairs
BD Europe
Capetown – November 2014

2. IVD Medical devices (IVDs) Are these all the same?
Medicines
Medical diagnostics
Pharmaceuticals
Medical Devices (MDs)
IVD Medical devices (IVDs)
Are these all the same?
Can they have one regulatory approach/framework?
PAHWP – Capetown November 29-30, 2014

3. Companion Diagnostics
DRUG
IVD
Medical Devices
In vivo use
In vitro use
Pharmaceutical
products
Active Implantable
Medical Devices
In vitro diagnostic
Medical Devices
Medical Devices
Borderline
Borderline
Combination
Products
PAHWP – Capetown November 29-30, 2014

4. Considerations why IVDs are different from other medical devices
In vitro diagnostic medical devices (IVDs) are used to conduct tests outside of the human body, often in a laboratory, on a specimen derived from the body.
IVDs are fundamentally different from other medical devices as they do not come into direct contact with the patient, making their performance and risk characteristics different. IVDs use human specimens, such as blood, tissue or urine, to carry out diagnosis, predictive testing, screening, and monitoring of conditions. These specimens are never reintroduced into the human body; however, they do provide valuable information regarding a patient’s health status.
Whereas medical devices are typically only evaluated on or in humans as a last step in their development, IVDs stand apart in that they are evaluated on human specimens derived from the human body as they are intended to be used throughout their entire development (from concept to final device). This sets IVDs apart from traditional medical devices.
PAHWP – Capetown November 29-30, 2014

5. Other considerations why IVDs are different from other medical devices
An IVD is rarely the sole determinant for diagnosis and treatment decisions. A combination of IVDs and/or an IVD in combination with other medical evidence is often used to come to a diagnosis or patient treatment decision. These combinations reduce the specific risk of the information provided by the IVD to the patient.
Human specimens used throughout the development of the IVD are usually de-identified left over or archived specimens, for example those available in a biobank whereas R&D for medical devices is done with bench testing and animal models.
PAHWP – Capetown November 29-30, 2014

6. Other considerations why IVDs are different from other medical devices
As human specimens are used throughout the whole development of the IVD, a considerable amount of information on the performance of an IVD is already gained from the manufacturer’s in-house performance studies which replicate to a large extent the conditions under which the IVD will be operating in the field (e.g interfering substances). This will provide data to support the claims and demonstration of safety and performance of the IVD and this reduces the risk. Therefore clinical evidence for medical devices and IVDs are fundamentally different.
The information that the test collects from the specimen during a study is typically not provided to patients or used in patient management decisions, removing direct consequences of the performance study. In rare cases where the information would be the sole basis for patient management decisions, additional measures are taken to mitigate any residual risk.
PAHWP – Capetown November 29-30, 2014

7. GHTF regulatory model SG 5 SG 3 SG 2 SG 4 What is a medical device
Definition of medical device and IVD medical device
What is needed to ensure
Safety and performance
Essential Principles of Safety & Performance
How to meet the Essential
Principles
Use of Standards (or other means)
What is needed to ensure
The safety of the product
Guidance on Clinical Evidence
SG 5
Labeling (including Instructions for use)
What level of Conformity
Assessment is appropriate
Risk based classification Rules – Class A, B, C or D
Quality System
Design Control Process
Full Technical Evidence
SG 3
Supporting Documentation
Submission file
Summary Technical File (STED)
Safe medical
device is placed
on the market
Post Market Vigilance and
Reporting Procedures
SG 2
Audit procedures and
protocols
SG 4
PAHWP – Capetown November 29-30, 2014

8. GHTF and IMDRF
All guidance documents developed by GHTF can now be found at – GHTF archive.
PAHWP – Capetown November 29-30, 2014

9. Regulatory Framework for IVDs and Access to affordable devices
The AHWP and the PAHWP agreed that
There is no need to develop a separate regulatory framework for affordable access to IVD medical devices or for IVD medial devices used in resource limited settings but
Where appropriate additional guidance could be developed to clarify certain aspects of the regulatory framework guidance documents with respect to access to affordable devices as well as the use in resource limited settings
PAHWP – Capetown November 29-30, 2014

10. Regulatory Framework for IVDs and Access to affordable devices
Aspects to be considered in such additional guidance for access to affordable IVD medical devices are :
Specific design requirements (clarify some of the Essential Principles with regards to affordable devices – eg. POC tests, stability, handling, storage and protection of reagents)
Faster access pathways (clarify some of the conformity assessment elements as well as agree on a common submission dossier (STED).
PAHWP – Capetown November 29-30, 2014

11. Regulatory Framework for IVDs and Access to affordable devices
Aspects to be considered in such additional guidance for access to affordable IVD medical devices are :
Different approach to clinical performance studies.
Labelling (clarify the link of some design elements important for affordable devices in the EP with the labeling of the product)
PAHWP – Capetown November 29-30, 2014

12. AHWP TC Playbook Scope & Content
PAHWP – Capetown November 29-30, 2014

13. Phased implementation Basic regulatory controls
Playbook Scope
Intended to guide AHWP member economies (and others) in the implementation of a model regulatory system
Applicable to countries with no framework or existing framework
International regulatory convergence
Highlights considerations e.g. phased implementation (basic controls to more advanced controls), national legal frameworks, resource needs, recognition of standards
Playbook Chapters
Recognition of Standards
Chapter 7
Registry / Database
Chapter 6
Manpower
Chapter 5
Phased implementation
Chapter 4
Legislation & policy framework
Chapter 3
Basic regulatory controls
Chapter 2
Introduction & Rationale for Harmonization
Chapter 1
PAHWP – Capetown November 29-30, 2014

14. Framework of Medical Device Controls
Regulatory model outlined in the Playbook is built on the foundation of the Global Harmonization Task Force (GHTF) guidance documents.
Quality management systems (QMS)
Post-market surveillance and vigilance
Definitions
& qualification of ‘medical device’ (MD)
Registration / licensing of MDs & dealers
Classification & conformity assessment of MDs
Oversight of QMS audits of dealers
Clinical investigation & clinical performance study controls
Basic Regulatory Controls
Advanced Regulatory Controls
Implementing a Regulatory Framework
PAHWP – Capetown November 29-30, 2014

15. Playbook Content: Considerations addressed
Implementation: where to start?
Is there a gauge of the market profile?
Effort to identify & engage
stakeholders
Other parties
(e.g. Maintenance,
Refurbishment)
End-users
Distributors
Manufacturers
Importers
PAHWP – Capetown November 29-30, 2014

16. Playbook Content: Considerations
Market Profile
What is the distribution of device types in the country? This is necessary to determine regulatory controls.
Are controls relevant across device types? E.g.:
Implants, surgical instruments, etc
IVDs
Medical software
Titrate controls – what depth of pre-market controls a device would need?
Higher Risk
Level of controls
Low Risk
Device Risk
PAHWP – Capetown November 29-30, 2014

17. Playbook Content: Considerations
Legislation & Policy
Robust Legislation & Transparent Policy Framework
Considerations when putting legislation and policies in place
Capacity Building in Regulations & Policy Development
Establish
Transitional steps
Gap analyses
of weakness in existing controls, e.g. devices on the market, pre-market controls, post market controls,
Identification & Engagement of stakeholders
Continuous refinement
PAHWP – Capetown November 29-30, 2014

18. Phased Implementation
Playbook Content: Considerations
Phased Implementation
Transition periods coherent in timing & sequence
Clear communication with stakeholders
Example of phased implementation steps: 7 6 5 4 3 2 1
PAHWP – Capetown November 29-30, 2014

19. Playbook Content: Considerations Manpower / Resource
To what extent are human resources sufficient to enable the Regulatory Authority to do its job?
Considerations to be made in planning resources / capacity building
Types of Regulatory Activities
Phase of Implementation
Capacity Building
Providing the tools to optimally fulfill responsibilities
Volume / Distribution of regulatory activities
Expertise
PAHWP – Capetown November 29-30, 2014

20. Registration Databases
Playbook Content: Considerations
Registration Databases
Knowing the purpose of databases is knowing what information to have in a database.
Gauge local profile of medical device activities & products
Identification of stakeholders
Using information to identify
trends
PAHWP – Capetown November 29-30, 2014

21. Playbook Content: Considerations
Essential Principles of Safety & Performance and Recognition of Standards
Essential Principles of Safety &Performance
GHTF: 6 general safety & performance principles
14 principles for non-IVD medical devices
12 principles for IVD medical devices
Purpose & benefits of standards
Mechanism for medical device
standards recognition
PAHWP – Capetown November 29-30, 2014

22. Playbook Elements Providing the Tools for Planning a Framework
Chapters 3 & 6
Chapter 3 & 6
Phased Implementation of Mandatory Controls
Manpower & Resource Determination
Development of Legislation & Policy
Training of Stakeholders & Staff
Full
Implemen-
tation
of a
regulatory
framework
Phased Implementation –Voluntary Phase
Continued
enhancement
Phased Implementation
Planning
Chapters 2 & 4
Chapter 5
Chapters 3 & 5
Chapters 3, 6 &7
Chapter 4
PAHWP – Capetown November 29-30, 2014

23. “Mindset”
This Playbook has not set out not a prescription of regulatory controls or pathway to implementation to countries.
It intends to provide considerations for a regulatory framework & build on foundation of existing resources
A house needs to..
Provide shelter
Protection from the elements
Security & comfort
Serve the needs of its inhabitants
PAHWP – Capetown November 29-30, 2014

24. Houses around the World
Adapted to the needs of the environment and landscape
What is the spirit behind implementing (this) regulatory control?
PAHWP – Capetown November 29-30, 2014

25. Final considerations for implementing regulatory controls for IVDs
Consider the differences between MDs and IVDs
Consider the implementation of more advanced pre-market controls only when you have a base of registration of your IVD medical device dealers and listing of the devices and you have or will have sufficient resources to implement the next level of controls
PAHWP – Capetown November 29-30, 2014

26. Final considerations for implementing regulatory controls for IVDs
If you move to more enhanced pre-market controls that include submissions consider the implementation of a regulatory submission file based on the GHTF STED document (also the WHO prequalification dossier is based on the STED document content).
Keep in mind that clinical evidence for IVDs is totally different than for MDs
PAHWP – Capetown November 29-30, 2014

27. Final considerations for implementing regulatory controls for IVDs
With regards to clinical evidence consider carefully the need for in country testing when the product is registered in the US or the EU, Australia, Canada and Japan as well as when there is a WHO prequalification
What will the additional in country testing add that this not available from the manufacturer’s testing or from the independent testing under the WHO prequalification?
PAHWP – Capetown November 29-30, 2014

28. Final considerations for implementing regulatory controls for IVDs
If you intend to create IVD regulations you might want to join the AHWP WG2 (pre-market for IVDs) – during 2015 and 2016 this WG will discuss all the GHTF documents related to IVDs and will publish them as AHWP documents
Meetings will provide in depth insides into the documents
Clarify what works and what does not
Help you in capacity building
PAHWP – Capetown November 29-30, 2014

29. Thank you! Benny Ons Director, Regulatory Affairs BD Europe
Tel:
November 29-30, 2014
PAHWP – Capetown November 29-30, 2014