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Reliance and Work-Smart regulation
Luther Gwaza PhD
Technical Officer
WHO/EMP/RHT/RSS, Email: [email protected]
17/05/2019| Title of the presentation 1
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If you want to go quickly, go alone. If
you want to go far, go together. ~
African proverb
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All pharmaceutical products, including
multisource products, should be used
in a country only after approval by
the national or regional authority.
Regulatory authorities should require
the documentation of a multisource
pharmaceutical product to meet the
following:
- GMP;
- Quality requirements; and
- Pharmaceutical product
interchangeability
3
WHA Resolutions: WHA 67.20 (2014); WHA 67.21 (2014); WHA63.12 (2010)
All pharmaceutical products,
including multisource products,
should be used in a country
only after approval by the
national or regional authority. Regulatory authorities should
require the documentation of a
multisource pharmaceutical
product to meet the following:
–– GMP;
–– QC specifications;
–– pharmaceutical product
interchangeability
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Manufacturers
(Mx)
Rejected (Rj)
Approved (Rx)
NRA
Standards & requirements
Processes
Laws & Regulations
HR capacity
QMS
Variations
Withdrawn (Rw)
Post-registration
monitoring
R(p)
Medicines Regulation Process Flow
IDEAL SITUATION
Healthier
populations
Robust Registration Systems
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Manufacturers
(Mx)
Rejected (Rj)
Approved (Rx)NRA
Standards & requirements
Processes
Laws & Regulations
HR capacity
QMS
Variations
Withdrawn (Rw)
Post-registration
monitoring
R(p)
Medicines Regulation Process Flow
REALITY
Registration processes not optimized
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Regulatory decision making
• Unilaterial or mutual recognition: mutual recognition is based on treaties or equivalent, providing maximal benefits but partial loss of sovereignty with regard to decision-makingRecognition
• Reliance on regulatory decisions performed by other competent and trusted agencies and/or cooperation/collaboration with other regulators to reduce the workload, with independent final decision-making
Reliance
Work-sharing
Joint reviews
• NRA makes independent decisions based on its own reviews or inspections
Normal/standard process
Regulatory cooperation based on convergence/ harmonization to improve the quality of decision making process
WHA resolution 67.20 (2014)
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Defining Reliance and Recognition
▪Reliance: act whereby a regulatory
authority in one jurisdiction may take
into account/give significant weight to
work performed by another regulator
or other trusted institution in reaching
its own decision.
▪Recognition: the routine
acceptance of the regulatory decision
of another regulator or other trusted
institution. Recognition indicates that
evidence of conformity with the
regulatory requirements of country A
is sufficient to meet the regulatory
requirements of country B.
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Decisions based on
information generated (100%)
by NRA
Verification, Secondary or tertiary reviews of
primary reports from other agencies e.g.
“SRA” or WHO PQ
e.g. EU decentralized
procedure, ZAZIBONA
e.g. Reference NRAs, WHO PQ, EU Mutual recognition.
NRA Registration
Pathways
Work-sharing
Joint activities
e.g. EU centralised
procedure, WHO-EAC joint
assessments
Reliance
NRA capabilities
Recognition
Full
assessment
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9
65% of children globally are immunized with WHO prequalified vaccines through the GAVI alliance
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PEOPLE ON ANTIRETROVIRAL THERAPY ACROSS THE GLOBE ARE TREATED WITH WHO PREQUALIFIED GENERIC MEDICINES
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How do WE get the quality assured product to
these patients faster, and more efficient?
How do WE ensure continued supply of quality
assured products post-registration?
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Facilitated pathways to “transfer” regulatory information & knowledge
WHO collaborative procedure
Vaccines: 2004Medicines: Started in 2012
Diagnostics: Pilot 2019Vector control: Pilot 2020
“SRA” collaborative procedure
• Sharing information (assessment, inspection and testing results) that serve as basis for national decisions – avoiding duplication.
• Voluntary participation – reference authorities, participating authorities and manufacturers/sponsors
Initiated in 2015European Medicines
Agency (EMA)Medicines and Healthcare
Products Regulatory Agency (MHRA)20 African NRAs
Regional networks
PRINCIPLES
African Medicines
Regulatory
Harmonization
Project (AMRH)
ASEAN SIAHR Project
**CRP-lite
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Published guidelines
http://apps.who.int/iris/bitstream/handle/10665/25533
8/9789241209960-eng.pdf?sequence=1
WHO Technical Report Series 996, 2016
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Published guidelines
WHO Technical Report Series 1010, 2018
http://apps.who.int/iris/bitstream/handle/10665/272452/978
9241210195-eng.pdf?ua=1
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Published guidelines
WHO Technical Report Series 1010, 2018
http://apps.who.int/iris/bitstream/handle/10665/272452/978
9241210195-eng.pdf?ua=1
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Concept of collaborative registrations (Reliance)
To support the national registrations,
regulators can benefit from already
organized scientific assessments and
inspections, if
• Having access to regulatory expertise
from trusted party (complete
assessment and inspection reports)
• Having the same product
• Having same essential technical data
• Understanding validity of B/R for local
environment**
• National legislation and sovereignty are
not affected
• Respect confidentiality of commercially
sensitive information
• Manage properly regulatory follow-up
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Access Market
Control
Recall the regulator'sdilemma…
Economic and
industrial
interests
Public health
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Manufacturers (Mx)
Rejected (Rj)
Approved (Rx)
NRA
Standards & requirements
Processes
Laws & Regulations
HR capacity
QMS
Variations
Withdrawn (Rw)
Post-registration
monitoring
R(p)
Medicines Regulation Process Flow
IDEAL SITUATION - WITH FACILITATED PATHWAYS
Healthier
populations
Reliance
Normal
Joint / Work-
sharing
Streamlined Registration processes
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IF
…
we share unredacted information
[assessments, inspections]
THEN…
NRAs can rely on the shared
information to facilitate national
decisions
THEN…• avoid duplications
• reduce regulatory
burden
• assess B/R in local
context
Timely access to
quality assured
products with
+B/R
Enhanced
NRA’s
oversight on
other products
& sites
Re-allocate resources
WHO PQ’ed
“SRA” approved Other
products
Relia
nce
Norm
al
path
way
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A modern regulator
Shared
regulatory
approach
Source: L Gwaza & G.N. Mahlangu (2015). Business Plan for the African
Medicines Agency
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• WHO National Control Laboratory Network for Biologicals 2017
• Use of WHO PQ’edlaboratories for testing of pharmaceuticals
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Laboratory Testing Services
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Lessons learnt with respect to facilitated pathways – for NRAs
1. Legislative prohibitions ???
2. Backlog in reviews (use of FIFO)
3. Lack of tools for recognition, reliance
or work sharing (one approach for all
applications)
4. Change management
1. Enabling laws
2. Risk based approach to registration
and Inspections
3. Guidelines
4. Procedures to guide staff
5. Staff awareness on reliance
approaches
6. Communication (internal and
external)
Barriers to reliance Key enablers for reliance
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“At a time in which medical product manufacturing is truly a global enterprise, there is much to be gained by partnering with regulatory counterparts to reduce duplicative efforts and maximize global resources while realizing the greatest bang for our collective inspectional buck. By partnering with these countries we can create greater efficiencies and better fulfil our public health goals, relying on the expertise of our colleagues and refocusing our resources on inspections in higher risk countries.” FDA Commissioner Scott Gottlieb, M.D. October 31, 2017.
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This is the Regulator's Dilemma!!...
“The need to maintain such a
delicate balance by applying
appropriate standards that are
scientifically justified and risk
proportionate to protect public
health while ensuring economic
and industrial interests are not
hindered”.
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The Future …..
Individual
NRAs with
specific
jurisdictions
Regulatory
Networks
“A cord of three
strands will not be
broken”
transition