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WHO support and Technical Assistance _
In-Vitro Diagnostics
Joint UNICEF, UNFPA & WHO Meeting with
Manufacturers and suppliers
UN City, Copenhagen, Denmark
24-27 September 2018
Dr Gaby Vercauteren
Senior Adviser, Regulatory Systems Strengthening Team
Regulation of Medicines and other Health Technologies
Copenhagen, Denmark 24 – 27 September 2018 1
2 Copenhagen, Denmark 18-21 September 2017
– The context
– Eligibility for technical assistance
– Principles & priorities for technical assistance
– Types of technical assistance and some data
– Past & future activities
Outline
The context
Every year, hundreds of millions of US dollars’ worth of
IVDs and medicines are purchased for distribution in
resource-limited countries
IVDs play a critical role in ensuring blood safety,
surveillance, diagnosis and treatment initiation
and monitoring
IVDs save lives, reduce suffering and improve health, but
only when they are of good quality, safe, effective,
available, affordable, acceptable and properly used
Copenhagen, Denmark 24 – 27 September 2018 3
WHO Prequalification – access to the global market
Prequalification listing linked to
• UN agencies procurement (WHO, UNICEF, UNDP,
UNFPA)
• The Global Fund QA policy
• MSF
• Strong collaboration with USG (USAID, CDC)
• National procurement / tendering specs
Range of products from which procurers can select
Copenhagen, Denmark 24 – 27 September 2018 4
Prequalification scope
HIV G6PD
malaria
HPV HCV
HBV
Cholera Syphilis
Expansion of PQDx scope over time
PQ eligibility
consultation – SAGE-IVD
6
Globalised industry sectors with outsourced production
Rapid emergence of new technologies
Increasing expectations on quality, safety and performance
Increasing pressure on human resources and increased
workload for regulators
Easy to operate tests/methods facilitate near patient testing,
hard-to-reach populations, non-lab environments
Changing IVDs global market trends
Copenhagen, Denmark 24 – 27 September 2018 7
PQ in a regulatory framework
Pre-market
Post-market
perfor
mance quality safety
Pre-2008
2008 - 2014
Post-2014
Changes
perfor
mance quality safety
reliance
WHO PQDx regulatory framework
Copenhagen, Denmark 24 – 27 September 2018 9
ISO and EN standards
GHTF / IMDRF
guidance documents
CLSI guidance
documents
PQ requirements
Prequalification: decision
Final prequalification outcome depends on:
• Results of dossier assessment and acceptance of action plan
• Results of inspection(s) and acceptance of action plan
• No level 5 nonconformities outstanding for either dossier or for
inspection
• Meeting the acceptance criteria for the laboratory evaluation
WHO PQDx Public Report is posted on WHO website and product is
added to the list of WHO prequalified products
Product is then eligible for WHO and UN procurement
What does PQ do differently to
GHTF/IMDRF
Requirements are based on the same set of standards – PQ is
aligned with internationally accepted practice BUT
Assess products' regulatory versions intended for the global market
• Where a stringently reviewed versions exist, they are often not supplied to
the global market – RoW versions differ from stringently assessed version
in Mx site, QC, labelling, key suppliers, composition, intended use etc.
Review aspects of particular relevance for resource-limited settings
• Risk assessment, stability, flex studies, labelling, training and support
network
• Take into account environment and user skills
What do we mean to regulate?
TESTS TESTING
? ? ? ? ?
POTENTIAL POINTS OF REGULATION
Background_ Rationale
Lessons from PQDx
Dossier submissions are improving, some still
substandard
– Unclear product identification
– Instruction for Use not conform requirements
– Insufficient control over key suppliers
– Quality control of lots
– Stability testing
– Performance studies
• Lack of evidence of performance in the intended
use setting
Copenhagen, Denmark 24 – 27 September 2018 13
Background_ Rationale
Lessons from PQDx
A portion of inspections have shown critical
nonconformities
– Ineffective quality management system
– Unsuitable facilities
– Lack of/ insufficient quality control of key product
components
– Traceability issues; from raw materials to lot release
– Inadequate documentation and procedures to verify
QC for lot release
– Inadequate procedures to handle customer
complaints
Copenhagen, Denmark 24 – 27 September 2018 14
Background_ Rationale
Lessons from PQDx
Lab evaluations
– Instructions for use_ often poor
– interpretation of results and reading times
– HIV RDTs lot to lot variation generally OK
– Customer service_ product identification
Alerts_ Recalls
– Manufacturers may not be well prepared to act
– Retained samples for a case of complaint " product
failure"
– Improve streams between_ user_ procurer _ Mx
Copenhagen, Denmark 24 – 27 September 2018 15
Background_ Rationale
Lessons from Mapping regulatory capacity for medical
devices _including IVDs
Regulation of IVDs is weak or lacking in many countries
– Africa, Asia,
– Recipient countries
– Countries with substantial manufacturing of UN
priority IVDs
Several countries have or are in the process of putting
regulations for medical devices in place
– i.e. South Africa, other African countries, India
– P.R. China is converging towards IMDRF guidance
Copenhagen, Denmark 24 – 27 September 2018 16
What do we want from you ?
Manufacturers
- IVDs of assured quality within the PQ scope to be
prequalified
- Investment in innovative IVDs adapted to LMIC countries
National regulatory authorities
- Implementation of regulation of IVDs aligned with IMDRF
- Pre- market
- Post market - So that in future WHO PQ and countries in the region
can rely on work that has been done satisfactory and
avoid duplication.
Copenhagen, Denmark 24 – 27 September 2018 17
Priorities for support & technical
assistance
Manufacturers/ Innovators of
– IVDs that are a priority and few products have been
PQ-ed
– Mx of priority IVDs that have potential, but previous
submission(s) to PQDx failed.
– Mx in stringently regulated countries_ products for the
Global market
Regulators/ Inspectorates / Notified bodies
– Countries with major production of IVDs for the global
market
• China, India, Korea
– Recipient Countries starting regulation of IVDs
Copenhagen, Denmark 24 – 27 September 2018 18
What can we do for you?
Copenhagen, Denmark 24 – 27 September 2018 19
What is the type of technical support that we
provide ?
• RSS advisory visits to manufacturers
- Gap analysis, assessement of readiness for PQ
• RSS trainings for manufacturers
- Topic specific trainings
• RSS trainings for NRAs
- Topic or function specific trainings
Copenhagen, Denmark 24 – 27 September 2018 20
RSS technical assistance
Copenhagen, Denmark 24 – 27 September 2018 21
PQDx requirements
Analyte-specific issues
Research and
development
The QMS, regulation
and certification
Types of technical assistance
Communication and advisory visits
– Gap analysis _innovators
Useful Tools
– Sample dossier_ e.g. CD4
– Training packages
– Guidance documents
Tailor made TA to Mx on specific technical issues
Training on general aspects and commonly
observed technical issues
Copenhagen, Denmark 24 – 27 September 2018 22
> Product dossier: > 3 sample dossiers (VL, EID and HIVST)
> several guidance documents to support dossier submissions > TGS1 Reference documents
> TGS2 Stability studies
> TGS3 Principles for performance studies
> TGS4 Sample dossiers
> TGS5 Product specific guidance
> TGS6 IFU
> TGS7 Flex studies
> TGS8 Specimen types
> TGS9 Test method validation
> IMDRF ToC (more granularity than STED)
> Inspections: > guidance documents
> TGS10 Quality control principles
> TGS11 Outsourcing and supplier mgt
PQDx technical guidance documents
Technical
assistance:
workshops
complemen
ting
guidance
(training
materials,
case
studies)
Set of
guidance
documents
and training
sessions to
assist
manufactur
ers
Overview of diagnostics-related Technical
Assistance and Laboratory services trainings Topics Activity Date Number trained
9 June _ am
2015
2016
2017
2018
▪ Advocacy meeting_ prequalification of Diagnostics, the importance of quality
▪ Main stakeholders meetings, manufacturers association, NACO, Un agencies representatives, CDSCO
▪ Major institutions
12-15 October
▪ NIFDC-WHO meeting PQ regulatory requirements and stability studies
▪ Commonly observed short comings in study design, analytical and clinical and stability studies, lot release testing, repositories, focus on HIV, Hepatitis B &C.
9- 11 June ▪ PQDx training Indian manufacturers ▪ Risk management and quality control for in-vitro
diagnostics
▪ PQDx observed non-conformities, detailed overview of risk management, risk analysis, risk report , risk mitigation, quality control of intermediate and final products
14 am June ▪ Advocacy meeting, ▪ Different Ministries and government officials, CDSCO, industry association
14 pm-16 June
▪ Workshop for Indian manufacturers: ▪ Regulatory requirements for performance & stability
studies for in-vitro diagnostic medical devices
▪ Commonly observed short comings in study design, analytical and clinical and stability studies, lot release testing, repositories, focus on HIV, Hepatitis B &C.
20-22 September
▪ PQDx training Chinese manufacturers ▪ Risk management and quality control for in-vitro
diagnostics
▪ PQDx observed non-conformities, detailed overview of risk management, risk analysis, risk report , risk mitigation, quality control of intermediate and final products
12-16 December
▪ Joint CFDA-WHO meeting .Dossier assessment of IVDs
▪ Exchange of information of processes and procedures , review and comparison of regulatory approaches.
8-10 August
▪ WHO training CDSCO ▪ Overview of PQ processes and procedures, dossier assessment, inspections and laboratory evaluations, Post market surveillance
26-27 October
▪ WHO meeting for Chinese manufacturers on regulatory requirements for performance & stability studies of malaria rapid diagnostic tests (IVD)
▪ Detailed overview of PQ requirements for malaria RDTs, GTS and TSS docu-ments, dossier requirements, inspections, analytical and clinical performance, requirements, Post market surveillance . participation of BMGF, China
12-14 December
▪ Joint CFDA/ WHO meeting : Dossier assessment of IVDs
▪ Update on PQ processes and procedures, and new TSS documents dossier assessment, inspections and new ISO 1348:2016 aspects post market surveillance
15-17 February
▪ India Pharma and Medical devices Forum. ▪ Advocacy and technical information sharing on prequalification of diag-nostics and implementation of the new rules. Presenting at the meeting and participating in several panel discussions and side events.
4-7 December
▪ WHO training CDSCO, inspectors ▪ PQ approaches to inspection, rating of non-conformities, inspection reports, corrective action plans
22-23 June ▪ 2nd Forum on China Biological Diagnostics ▪ Presentation on Prequalification of diagnostics and global market requirements
21-24 August
▪ WHO-CFDI training for inspectors ▪ PQ approaches to inspection, rating of non-conformities, inspection reports, corrective action plans 30
29
24
28
30
23
20
35
40
20
40
750
Planned
700
Expected outcomes
Improved quality & safety of products
Product better responding to the needs of the global market
Positive spin off effect on all products manufactured, at a site and/or
by a company
More efficient prequalification process:
– shorter timelines & higher success rate
Improved regulatory capacity in key countries
Thus :
More quality diagnostics available and accessible to
improve the health of people in low- and middle-income
countries
Copenhagen, Denmark 24 – 27 September 2018 25
Future plans
• To continue the activities, but also further
expand involvement of third parties.
• To involve more local players to expand the
reach out to local manufacturers
• India and P.R. China
• To foster regional regulatory networks for IVDs
• To build trust with PQDx and amongst each other
• Mapping of specific training needs for NRAs and
affiliated Institutions
Copenhagen, Denmark 24 – 27 September 2018 26
Contact us
Contact us by email
vercautereng@who.int
By emailing diagnostics@who.int
http://www.who.int/prequalification
Sign up to our mailing list
Check our website
Questions
Copenhagen, Denmark 24 – 27 September 2018 28
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