Transcript Regulators` Group Report (Prof. John Skerritt)

Regulators’ group report
John Skerritt
National Manager
Therapeutic Goods Administration
Australian Department of Health
Several priorities identified at the March ‘14 meeting
of AQMTF required action by medicines regulators
So……AQMTF requested that a Regulators’ Group be
established to develop options for consideration by
AQMTF for:
- improving the availability of, and access to, quality
medicines and diagnostics
- help to contain the spread of artemisinin resistance
- strengthen capacity to monitor quality of products and to
take action when substandard products are detected
We recognised that much high quality
analysis has already been done on priorities
for better malaria control, access to quality
medicines and managing drug resistance
e.g. by WHO, Global Fund, governments,
donors and APLMA itself
Major reports were reviewed
A strongly-held view emerged that the role of the
Regulators’ Group was not to duplicate
recommendations of these studies, but from a
regulatory perspective to provide more detailed
advice about specific priorities and actions
In most cases – such as improving the access to
quality antimalarials - it was agreed that regulatory
action would only be part of a potential solution
Participants in the
Regulators’ Group meeting
in Bangkok (May 14-15)
included Regulators and
Public Health
representatives from
Australia, India, Malaysia,
Cambodia, Japan, Thailand,
Lao People’s Democratic
Republic, Philippines,
Singapore, Viet Nam,
Indonesia, WHO,
Population Services
International and DFAT
Australia
.
The Regulators’ group is co-chaired by Australia and India
in alignment with the AQMTF
It took a practical “ground-level” view
rather than a “high level” general view
.
A two stage survey of countries was
initially carried out
- of current regulatory frameworks within each country
as they relate to the regulation of malaria products
- broader issues on access to malaria products, and the
roles of different organisations in providing access
Responses were received from 14 countries: Australia,
Brunei, Cambodia, India, Indonesia, Japan, Lao PDR, Malaysia,
Myanmar, PNG, Philippines, Singapore, Thailand and Viet Nam
The surveys: Market Authorisation
- All respondents indicated that it is a legal requirement to
license antimalarial medicines in their country before supply
- But over 30 different medicines/combinations and more than
90 different strengths/dose forms had been licensed
- Only 8 of these align with the WHO Essential Medications List
- Regulators identified 14 further medicines or combinations
known to be supplied in their countries without licence
- Only a few countries regulate Rapid Diagnostic Tests (IVDs)
The surveys: Medicines Quality
- All regulators indicated that they had responsibility for
monitoring quality of medicines supplied in their country
- Often in partnership with other government authorities,
though some indicated that they had limited capacity
- SSFFC medicines were recently identified in four countries
- Regulators stated that their postmarket or pharmacovigilance
roles and compliance and enforcement powers were usually
less well defined than their premarket authorisation role
Structure of the report
KEY AREA 1: Ensuring that the
quality of malaria
commodities is consistent
with international standards
.
Recommendation 1: Implement specific regulatory
market authorisation actions to improve access to the
most appropriate antimalarial medicines and diagnostics
Recommendation 2: Establish fast-track regulatory
approval mechanisms to encourage market availability of
fixed dose combination formulations (rather than coblistering) and combinations of new active ingredients, to
improve patient compliance and provide flexibility for
addressing changes in antimalarial resistance
Artemesinin: not a silver bullet if used
alone orally
Recommendation 3: Implement regulatory actions to
improve access to appropriate Rapid Diagnostic Tests
for the diagnosis of malaria
Recommendation 4: Undertake action to withdraw
inappropriate malaria treatments
Recommendation 5: Implement communication
initiatives to improve quality use of antimalarials
KEY AREA 2: Removing oral
artemisinin monotherapy and
Substandard/ Spurious/ Falselylabelled/ Falsified/Counterfeit
(SSFFC) products
.
Removing artemisinin monotherapies
Recommendation 6: Use the range of regulatory options
permitted by law in each country to a greater extent, and
where required strengthen the legal basis of regulatory
powers, to support the halt of oAMT
Recommendation 7: Implement systematic programs for
monitoring the quality of ACT particularly in districts
where artemisinin resistance has been detected/suspected
Recommendation 8: Use robust commodity market
assessment and monitoring methods to inform regulatory
policy and practice across the region
KEY AREA 3: Strengthening
regulatory capacity and
regional collaboration of
National Regulatory Authorities
with responsibility for malarial
medicines and diagnostics
Recommendation 9: Strengthen regional collaboration
between NRAs to build capacity and increased
convergence of good regulatory practices
Recommendation 10: Where possible, work through
existing national and regional initiatives to deliver
capacity building support to assist countries with
monitoring quality of malaria diagnostics and medicines
Recommendation 11: Governments to provide
adequate support, powers and investment to National
Regulatory Authorities
KEY AREA 4: Improving access
to and supply of quality
preventative measures and
therapies, particularly for highrisk groups
.
Recommendation 12: National Regulatory Authorities
to more proactively work with other government
agencies, malaria control programs and stakeholders,
recognising the particular vulnerability of mobile and
remote populations and the prevalence of artemisinin
resistance in border regions
From recommendations to actions
- Supporting the 12 recommendations are 42 proposed
actions - 24 of which are prioritised for immediate action
- For each action, ‘Lead’ or ‘Support’ roles are suggested
- Only some of the actions are relevant for particular
stakeholders, such as public health programs, WHO,
government policy makers, donors and regulators
- Context for implementing actions provided in the report
- Anticipated that the specific actions could guide future
investment by governments, WHO and donors
.
Recommendation 1: Implement specific regulatory market
authorisation actions to improve access to the most appropriate
antimalarial medicines and diagnostic tools
.
IMMEDIATE ACTIONS
• Ensure that all relevant WHO prequalified essential medicines
and diagnostics have market authorization in affected countries
• Fast track regulatory evaluation for market authorisation of
equally effective but less expensive “partner” antimalarial
components of Artemisinin Combination Therapies (ACTs)
• NRAs to work with National Malarial Control Programs and
Procurement Agencies to develop quality standards consistent
with nationally/internationally recognised requirements to
support procurement and that only products of appropriate
quality are procured, irrespective of funding source
= lead role required by National Regulatory Authorities (NRAs)
Recommendation 1 (continued): Implement specific regulatory
market authorisation actions to improve access to the most
appropriate antimalarial medicines and diagnostic tools
LATER ACTIONS
• Work with industry and public health systems to ensure appropriate
ACTs have market authorisation in each country, particularly those
required to address current or potential resistance
• Ensure that only malaria medicines at the doses recognised in
clinical treatment guidelines are approved by NRAs
• For countries where regulatory powers currently only extend to
medicines use within the public health system, extend these powers
to medicines used in the private and informal sectors
Recommendation 2: Establish fast-track regulatory approvals to
encourage availability of fixed dose combinations (and combinations
of new active ingredients) to improve patient compliance and
provide flexibility for addressing changes in antimalarial resistance
IMMEDIATE ACTION
Recommendation 3: Implement regulatory actions to improve
access to appropriate Rapid Diagnostic Tests (RDTs) for malaria
LATER ACTIONS
• Develop more consistent national regulatory frameworks to ensure
that RDTs are assessed to nationally/ internationally agreed
standards for performance and stability, and that instructions for
use are appropriate
• Develop a capacity building program to establish local mechanisms
for assessing diagnostics and their quality management by building
on WHO prequalification of in vitro diagnostics
Recommendation 4: Undertake action to withdraw inappropriate
malaria treatments
IMMEDIATE ACTIONS
• Where possible, NRAs to withdraw the registration of medicines
that are still registered for malaria but no longer recommended
because of safety, known resistance or lack of efficacy
• Together with public health authorities, NRAs to review the drugs
currently authorised to ensure registered doses are appropriate
and consistent with WHO guidelines/ National Drug Policy
• Revoke licences for products containing sub therapeutic levels of
antimalarials or irrational combinations of active ingredients
LATER ACTIONS
• Ensure that ineffective antimalarials are no longer included in
national formularies or national essential medicines lists
• Discourage (and deregister where possible) “cocktails” of
inappropriate medicines used for malaria prevention or treatment
Recommendation 5: Implement communication initiatives to
improve quality use of antimalarials
LATER ACTIONS
• Strengthen communication about the appropriate use of products
to doctors, pharmacy and clinic workers and patients through
– the process of formal approval of product / consumer
medicines information by the regulator
– as well as broader public communication activities
Recommendation 6: Use the range of regulatory options permitted
by law in each country to a greater extent
Where required, strengthen the legal basis of regulatory powers to
support the halt of oAMT along the supply chain
IMMEDIATE ACTION
• NRAs to ensure sufficient regulatory power exists and enforcement
actions are implemented to allow for:
– forbidding or withdrawing market authorisation for oAMT
– suspension of manufacture and import licences
– Forbidding/ withdrawing export licenses for oAMT manufacturers
– active monitoring of premises of oAMT and SSFFC drugs and RDTs
– recall and destruction of oAMT and SSFFC finished products
LATER ACTION
• Develop communication programs aimed at consumers, healthcare
providers and industry on hazards of oAMTs and substandard and
counterfeit medicines, including how to report these to authorities
Recommendation 7: Implement systematic programs for monitoring
quality of Artemesinin Combination Therapies (ACTs), particularly in
districts where artemesinin resistance has been detected/suspected
IMMEDIATE ACTIONS
• Increase post-market surveillance of ACTs across the full
distribution chain including periodic re-testing of licensed products
• Increase the focus on product shelf-life and storage of medicines
and RDTs as a contributor to their substandard performance
• Regularly and systematically report incidents of suspected cases of
SSFFC products and actions taken through WHO rapid alert systems
• Ensure adequate access by NRAs to accredited analytical testing
facilities. Where facilities do not exist (and for complex analyses),
develop mechanisms for sending samples to partner countries
• Work with regional governments to streamline importation of
suspect samples for testing in accredited regional laboratories so
that timely regulatory action is possible
Recommendation 8: Use robust commodity market assessment and
monitoring methods to inform regulatory policy and practice across
the region
IMMEDIATE ACTIONS
• Utilize rapid supply chain assessments and targeted outlet surveys
to generate a consistent baseline picture of the total antimalarial
product market across the region
• Analyze baseline data to ascertain if time-limited price subsidy
interventions are warranted (in conjunction with regulatory
enforcement) to accelerate displacement of oAMTs and improve
access to quality assured ACT and RDTs
LATER ACTIONS
• Assess the impact of interventions, regulatory and market-based,
on access to quality antimalarials and diagnostic relative to SSFFC
products through outlet surveys and real-time monitoring
Recommendation 9: Strengthen regional collaboration between
NRAs to build capacity and convergence of good regulatory practices
IMMEDIATE ACTIONS
• Fast-track national registration of an agreed list of WHO
prequalified medicines through sharing of assessment reports
generated by the WHO Prequalification process, if permissible
under the regulatory framework of the respective country and
worksharing on drug applications between countries
• Develop mechanisms for collaboration between regulators on
GMP inspections of local manufacturers of antimalarials
• Strengthen collaboration with major “stringent” regional
regulators and WHO Prequalification programs, and increase
investment in training programs
• Support efforts for harmonisation of regulatory requirements and
processes for market authorisation of rapid diagnostic tests
Recommendation 9 (continued): Strengthen regional collaboration
between NRAs to build capacity and convergence of good regulatory
practices
IMMEDIATE ACTIONS
• Support cross-border coordination of regulatory and enforcement
actions, especially as they relate to high-risk and hard-to-reach
populations
• Strengthen local and regional exchange of intelligence on
counterfeit and substandard products
• Recognise and endorse the WHO Member State Mechanism on
SSFFC workplan, identifying priority actions and resources for NRA
participation. Translate SSFFC norms and standards into use
Encourage multi-country rather than single country
involvement in major regional and donor antimalarial initiatives
Existing processes and governance mechanisms should be
utilised wherever possible
Recommendation 10: Where possible, work through existing
national and regional initiatives to deliver capacity building support
to assist countries with monitoring and testing the quality of malaria
diagnostics and medicines
IMMEDIATE ACTIONS
• Strengthen capacity for post-market surveillance of malaria
diagnostics and medicines across the distribution chain, including
manufacturers, importers, wholesalers and health posts
• Specific actions include:
– Strengthening pharmacovigilance capacity including reporting
of treatment failure and adverse events
– Strengthen oversight of manufacturers and the supply chain
through greater GMP inspection capacity
– Improved laboratory testing capacity and use of consistent lab
accreditation standards for testing of suspect products
– Training in regulatory compliance and enforcement
Recommendation 10 (ctd): Where possible, work through existing
national and regional initiatives to deliver capacity building support
to assist countries with monitoring and testing the quality of malaria
diagnostics and medicines
LATER ACTIONS
• Strengthen market authorisation roles for both medicines and
Rapid Diagnostic Tests (RDTs) by increasing the capacity of NRAs to
work in collaboration with the WHO prequalification program
• Explore potential for formal worksharing between regional NRAs
• Develop regulatory frameworks for market authorisation of in vitro
diagnostics (which include RDTs)
• Develop the capacity of NRAs to produce communication materials
and education programs on appropriate use of antimalarials and
diagnostics and the dangers of poor quality medicines
• Evaluate portable technologies such as the USFDA rapid CD3 device
for the detection of counterfeit medicines
RDT performance has not been well
addressed thus far by Regulators…
Recommendation 11: National governments to provide adequate
support, powers and investment to NRAs
IMMEDIATE ACTIONS
• Strengthen and formalise linkages between NRAs, public health
authorities and national malaria control programs, including
involvement of both functions at National and Regional meetings
• Review the adequacy of powers available to NRAs, with a view to
putting in place powers with similar intent in different countries to
enable coordinated responses to SSFFC and oAMT medicines
• Ensure NRA functions receive a sufficient share of funding within
national budgets and international programs to enable these
recommendations to be adequately implemented
LATER ACTIONS
• Investment in technical capacity building within NRAs
Recommendation 12: NRAs to more pro-actively work with other
government agencies, malaria control programs and stakeholders,
recognising the vulnerability of mobile and remote populations and
the prevalence of artemesinin resistance in border regions
LATER ACTIONS
• NRAs to work with:
– Public health authorities when they receive information on
adverse events, treatment failure or resistance to medicines
– Police where smuggling of oAMTs across borders is suspected
– National medical research centres, to develop strategies for the
use of diagnostic tests to detect artemesinin resistance markers
and integrate guidelines for alternative therapy into medicines
product and prescribing information as required
• Strengthen the involvement of NRAs in communicating and
managing shortages of malaria medicines and RDTs – e.g. by
implementing streamlined regulatory approaches to facilitate shortterm access to antimalarials approved by another regulator
Conclusions and Next Steps
- To date, regulators have not usually been engaged
consistently with malaria issues and responses by
regulators to issues such as oAMT resistance have been
fragmented
- Implementation of several of the recommendations
would have a broader impact in strengthening access to
quality medicines in the Asia-Pacific
- Importance for building on existing national and regional
regulatory, health and malaria control programs rather
than creating new centres or programs
- Recommendations and actions will need to be integrated
with other outputs from AQMTF /APLMA