Post on 11-Jul-2020
WHO efforts to promote good regulatory and good reliance practices
Samvel Azatyan MD, PhD.Acting CoordinatorRegulatory Systems Strengthening [RSS]Regulation and Prequalification Department [RPQ]World Health OrganizationE-mail: azatyans@who.int
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Improving the Response of Global Public Health in a Fast-changing WorldJoint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers of in-vitro diagnostic products, vaccines & immunization devices, finished pharmaceutical products, active pharmaceutical ingredients, contraceptive devices and vector control products2−5 December 2019, UN City, Copenhagen, Denmark
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Access to medical products – global challenge
• In many low- and middle-income countries essential medicines are not always readily available and accessible;
• WHO estimate is that one third of the world’s population have no access to essential medicines (and more than half in some areas);
• Lack of essential medicines contributes to disparities in health and life-expectancy between low-income and high-income countries;
• Reasons for limited/insufficient access are different but one of them is inadequate regulatory capacity and lack of collaboration and work sharing in medicines regulation.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
It is all about the time..
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One child under age 15 died every five seconds in 2018UN Inter-agency Group for Child Mortality Estimation
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
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 regulatory authority.
• Regulatory authorities should require the documentation of a multisource pharmaceutical product to meet the following:
• GMP;• Quality requirements; and• Pharmaceutical product interchangeability
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Medicines Regulation Process Flow (1)
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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)
IDEAL SITUATION
Healthier populations
Robust Registration Systems
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Medicines Regulation Process Flow (2)
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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)
REAL SITUATION
Registration processes not optimized
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Gap in Regulatory Capacity
• ≈30% of NMRAs globally have limited capacity to perform core regulatory functions
• Regulatory capacity gap between different countries (low- and high-income) in terms of:
• Human and financial resources;• Regulatory functions effectively performed;• Expertise available for fulfilling regulatory functions;• Availability of proper systematic training for regulators;• Applying quality management principles.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Need for reliance – LMIC example
Summary observations:• Guidelines and assessment procedures are
not up to international standards and are often of an administrative rather than technical nature;
• Inadequate resources severely limit technical assessment of dossiers;
• In spite of resource constraints only few countries rely/refer on decisions made by other regulators (such as stringent NMRAs or by the WHO PQ);
• Some countries had restrictive regulations not allowing reliance..
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26 country study
in Africa
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
The concept of regulation is changing (1)
NRAs are mandated in their jurisdictions to ensure timely access to safe, effective and quality medical products - in line with international standards;
There is no clear vision or policy about HOW to set up regulatory systems in times when it is unrealistic to manage all functions in one national setting for most regulators – globalization of regulatory science;
New products are likely more complex and sophisticated – demanding advanced health systems and "quality use“;
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
The concept of regulation is changing (2)
Questions to answer: Can all national regulators assess and inspect all
product applications coming to their markets? Does repetitive assessments and inspections give
any added value? If they prefer not to repeat the work done - how to
build confidence in scientific assessments/ inspections carried out by other parties?
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
The concept of regulation is changing (3)
Health systems and health providers are varying in “strength” between countries:
• Not all new products coming to the markets equally fit for all types of health systems and health providers available;
• Benefit/risk assessment is not always taking into consideration the health systems in which product is to be launched?
• Not always we know what exact competencies are needed for regulators to be able to perform their functions.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Draft WHO GRP Guidelines
• The guideline outlines internationally accepted principles of GRP and describes how they may be implemented;
• Is intended for NRAs and other related institutions responsible for the formulation of health policies, laws, regulations and guidelines;
• Will assist WHO Member States in the implementation of GRP, both in establishing new regulatory systems for medical products and in improving the existing ones.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Framework of Best Practices for Regulation of Medical Products
GRP Umbrella Statement
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Performance Measurement
Good Reliance Practices
Good Review
Practices
Regulatory Pathways –Good Registration
Practices
Good Guidance Practices
Good Governance
Practices
QMS for Regulatory Authorities
Global Regulatory
Model
Models for Regulatory
Systems
Good Regulatory Practices
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Good reliance practices guideline
Scope:• The guideline is intended for national regulatory authorities and
to be applied across processes involving the regulation of pharmaceuticals products, including small molecule, biologics and vaccines;
• These processes and their respective frameworks and policies include, but are not limited to:
• the management of clinical trial applications,• product applications• post-approval activities.
Format of the document:• Expected to be a light and practical instrument – deriving from
the “parent” GRP guideline
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Reliance facilitates good quality decisions:WHO efforts • Promoting good governance and transparency in medical
products sector – GRP process;• Promoting and facilitating building up national regulatory
systems as part of overall health systems strengthening;• Promoting functional/adequate national regulatory systems
as important contributor to achieving universal health coverage and able to address public health priorities;
• Supporting regulatory workforce development – Global Regulatory Curriculum;
• Promoting regulatory cooperation, convergence and harmonization;
• Promoting work sharing – based on reliance on the work of trusted authorities to inform regulatory decision-making.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Timely access to medical products – never-ending challenge • Patients/consumers – wherever they are – deserve access to
quality assured medical products with positive benefit-risk characteristics - UHC;
• Today’s reality and demand: to generate quality national decisions regulators globally MUST collaborate and MUST take into consideration the information available from other regulatory authorities;Not using the outputs and outcomes from other regulatory
authorities
Lost opportunity, duplication of efforts, increased regulatory burden and waste of scarce resources
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Options for achieving a regulatory decision
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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-sharingJoint 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)
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Regulatory cooperation hierarchy
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Convergence &
harmonization
Convergence &
harmonization
Recognition
Reliance
Work-sharing
Information-sharing
Reliance
Reliance
Recognition
Recognition
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Reliance and Recognition
Often-used terms in regulatory documentation, but lack formal definition
• Reliance: is the act whereby a regulatory authority in one jurisdiction may take into account and give significant weight to evaluations performed by another NRA or other trusted institution for reaching its own decision. The relying authority remains responsible and accountable for decisions taken, even when it relies on the decisions and information of others.
• Recognition: the routine acceptance by the NRA in one jurisdiction of the regulatory decision of another NRA or other trusted institution. Indicates that there is a sufficient evidence of conformity with the regulatory requirements of country A to meet the regulatory requirements of country B.
• In all cases the sovereignty of regulatory decision remains in the hands of national regulators.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Registration Pathways available for NRAs
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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.
Work-sharing
Joint activities
e.g. EU centralised procedure, WHO-EAC joint
assessments
Reliance
NRA capabilities
Recognition
Full assessment
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
When can reliance be used?
Some elements of regulatory oversight can be shared • Evaluation of quality, efficacy and safety;• Inspections;• Testing.Other elements of regulatory oversight must be local• Licensing decision;• Local manufacturing oversight;• Pharmacovigilance;• Appropriate distribution controls (stability and cold
chain)• Product security.
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Facilitated pathways to “transfer” regulatory information & knowledge
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WHO collaborative
procedureVaccines: 2004
Medicines: Started in 2012Diagnostics: Pilot 2019
Vector control: Pilot 2020
“SRA” collaborative procedure
• Sharing information / expertise (assessment, inspection and testing results or expertise) 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
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
IDEAL SITUATION – with facilitated pathways
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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) Healthier populations
Reliance
Normal
Joint / Work-sharing
Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
Conclusions:
• Not a single regulator anymore can fulfil all regulatory work alone;
• The future of medical products regulation is in convergence/harmonization, collaboration, work-sharing and networking – based on reliance;
• Regulators are starting to operate more as a functional network rather than individual players, and individual players focusing on where they can give the best added value;
• The new “regulatory work-sharing slogan” could be:
Do yourself only what you can do well,and benefit from what others could do better..
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Joint UNICEF, UNFPA and WHO meeting with manufacturers and suppliers2−5 December 2019, UN City, Copenhagen, Denmark
www.who.int/medicines
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