“strengthening the regulation of medical products through networking, cooperation ... ·...

WHO Technical Briefing Seminar Essential Medicines and Health Technologies (WHO/EMP)

“Strengthening the regulation of medical products through networking, cooperation and harmonization”

12 October 2017

Gabriela Zenhäusern I Technical officer I RHT/RSS/RNH

12/10/2017 | “Strengthening the regulation of medical products through networking, cooperation and harmonization” 2

Access to medicines – global challenge (1)


Access to medicines – global challenge (2)

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);

Poor uptake of new and existing health solutions costs millions of lives across

low-income countries;

Lack of essential medicines contributes to disparities in health and life-

expectancy between low-income and high-income countries;

One of the reasons of limited access is the insufficient regulatory capacity in

the countries and lack of harmonized approaches for regulation of medical

products.

Regulatory convergence and harmonization initiatives


Convergence and harmonization efforts should in theory diminish duplication, creating a

"common language" for decision-making and facilitating cooperation, work-sharing and

eventually reliance or recognition


Areas of convergence and harmonization

Clinical trials –

Harmonization of requirements for applications to conduct Clinical Trials

Recognition of Good Clinical Practice (GCP) audits

Clinical trial registries

Medical product registration –

Harmonization of technical guidelines & registration requirements

Reliance of Good Manufacturing Practices (GMP) audits & dossier assessments

Work-sharing of dossier assessments

Post-market surveillance activities –

Information-/work-sharing of Adverse Drug Reactions/safety assessments

Work-sharing/reliance on product testing results

Information-sharing on counterfeit medical products, product defects and GMP non-compliance of manufacturers


Sovereignty in regulatory cooperation

Engaging in regulatory cooperation doesn't mean a loss of national

sovereignty / autonomy;

Use of collaborative and cooperative mechanisms, (e.g., joint

assessments of marketing applications or sharing of inspection reports),

does not imply collaborative decision-making!

In all cases the regulatory decision itself remains firmly in the hands of

sovereign nations.


WHO views on Regulatory Cooperation


Reliance and Recognition

Both reflect "taking account of’’ the output of other regulatory authorities;

Increasing prevalence/necessity, even with most mature/resourced NRAs;

Prerequisite: regulatory system and functions that can then be the object of reliance or recognition;

May be both unilateral or mutual

NB: sovereignty maintained in both cases

Reliance Recognition

Reduction: streamline/reduce internal work

Replacement: operationally, rely on decisions


Why WHO Supports Regulatory Convergence and Harmonization?

NMRAs National Government

Donor Community

Manufacturers (Local and

International)

Patients / consumers

• Greater process transparency • Reduced regulatory burden • Shorter time to approval • Greater incentive to prioritize dossier

submissions • Improved access to regional markets

• Potential for savings/greater reach via generic equivalents and increased competition

• Healthcare resources can be better managed

• Improved public health outcomes

Higher patient reach for a given level of support

• Increased capacity • More timely & cost effective

evaluation processes • Greater regulatory network, sharing

of best practices & experiences • More effective medicines control

• Quicker access to more affordable medical products of assured quality, especially for priority medicines

• Improved assurance that available medical products are safe


Regional Cooperation – regional efforts

ASEAN SIAHR Project

PANDRH

African Vaccine Regulators Forum (AVAREF)

African Medicines Regulatory Harmonization Project (AMRH)

Objective of EAC Medicines Regulatory Harmonization (MRH)

To harmonize medicines regulation in the EAC Partner States in order to increase the rapid availability of

essential medicines in the region

EAC MRH Project evolution and expansion

Project proposal on harmonization and strengthening of regulation of medical devices and diagnostics

Project proposal on harmonization and strengthening of pharmacovigilance systems for medicines,

health products and other health technologies in the EAC partner states

Project proposal on harmonization of regulatory framework for control of clinical trials on medical

products, vaccines and health technologies

East African Community (EAC)

12/10/2017 | “Strengthening the regulation of medical products through networking, cooperation and harmonization”

Joint assessments



A procedure for joint assessment by the National Medicines Regulatory Authorities

(NMRAs) of the EAC Partner States in the assessment of selected medicinal products,

inspection of their respective manufacturing site(s) followed by national approval of

jointly accepted medicinal products.

Participants: Representatives from the EAC secretariat, the technical working group of the

Medicines Evaluation and Registration, assessors from the EAC Partner States,

representatives from the World Bank, Swissmedic and WHO

5th EAC joint assessment, Entebbe, Uganda 18 – 22 April 2017

6th EAC joint assessment, Dar es Salaam, Tanzania 18 – 21 July 2017

7th EAC joint assessment, Dar es Salaam, Tanzania, dates tbc

Reduced the registration timelines

Facilitated capacity building

Helped to learn how "to listen and to speak to each others"

Trust building – among EAC regulatory experts

Expensive by itself but with a huge potential for future savings

Can be considered as one of the possible models for application in low- and middle-income countries/ groupings

Joint assessments – Potential expectations for the future




Zazibona Founding Member States: Zambia – Zimbabwe – Botswana – Namibia

Active Participating Member States

Botswana

DRC

Namibia

South Africa

Zambia

Zimbabwe

Observer Member States

Angola

Seychelles

Swaziland


Zazibona

Regulatory collaboration based on the exchange of assessment and

inspection reports for generics

to reduce regulatory workload

to accelerate registrations of needed products

to develop mutual confidence in regulatory collaboration

to test the mechanism of co-operation among regulatory authorities for

potential use by others

to improve information sharing and/or networking

to identify priority areas for regulatory harmonization

As example of regulatory collaboration


Zazibona

Agreement of assessors on products selected for work-sharing

− Submitted for approval in at least 2 countries

− Therapeutic relevance

− Applicant's agreement with information sharing

Agreement on leadership in assessment ("rapporteur")

Rapporteur compiles the draft assessment report and questions to applicant for

comments.

− Comments and questions to applicant consolidated in meetings of assessors.

− Meetings combined with trainings on specific subjects

− Areas of 'disharmony' identified and solutions proposed

− Outcomes and recommendations communicated to HoA

How it works


Zazibona

Agreed list of questions circulated to national applicants (possible to combine

with country specific issues) to be responded to all countries concerned

Rapporteur leads assessment of applicant's responses, updates assessment

report and suggests outcomes to participating countries for submission to

authorities for further processing

NRAs in each country decides

Collaboration among inspectors is at the planning stage to conduct joined

inspections in the near future

How it works


Zazibona Real work sharing in practice !

Since

2013


WHO Collaborative procedure

Voluntary

Product and registration dossier in

countries are 'the same' as prequalified

by WHO

Shared confidential information to

support NRA decision making in

exchange for accelerated registration

process

'Harmonized product status' is

monitored and maintained


Key principles



Mechanism


Marketing

authorisation

Submission

NRA WHO Prequalification

Assessment

and inspection

reports

Manufacturer


Current Status by WHO PQ product stream


Decide on use of the process for individual products

− Recognize

− Verify

− Organize risk/benefit second review and inspections

− Consider in decision making

− Use as quality assurance of national assessment and decision

Conclude differently from WHO Prequalification - justify

Benefit from shared information for harmonization and training

Accelerate the national decision and keep WHO informed about the national decision

Options for participating regulators



Time to registration (Medicines) – Including regulatory time and applicant time


(2013 – 2017 to date, n=215)


As at 12 May 2017

Median time to registration (Medicines)



As at 12 May 2017

*Including regulatory time and applicant time

National Regulatory Authorities (NRA)

− Having data well organized in CTD in line PQ requirements

− Availability of WHO assessment and inspection outcomes to support national

decisions and save internal capacities

− Opportunity to learn from PQ assessors and inspectors

− Demonstrating NMRA efficiency

− Having assurance about registration of 'the same' medicine as is prequalified

− Quality control by same methods and specifications

− Easier post-registration maintenance

− Having a model process for mutual co-operation in registrations

WHO

− Prequalified medicines are faster available to patients

− Feed-back on WHO prequalification outcomes

Win-win outcomes for all stakeholders



Manufacturers

− Harmonized data for PQ and national registration

− Facilitated interaction with NMRAs in assessment and inspections

− Accelerated and more predictable registration

− Easier post-registration maintenance

Procurers

− Faster start of procurement and wider availability of PQ medicines

− Assurance about 'the same' medicine as is prequalified (website)

Win-win outcomes for all stakeholders



29 https://extranet.who.int/prequal/content/collaborative-registration-faster-registration

https://extranet.who.int/prequal/content/collaborative-registration-faster-registration








The 5th Annual Meeting of focal points

of the WHO collaborative procedure

Accra, Ghana, 25 - 26 November 2017

Side meeting on CRP of OCV vaccine


True harmonization is NOT just development of common documentation

Appropriate legislative and regulatory requirements:

Legal framework to define the basis and conditions for collaboration and work sharing/acceptance of information and decisions;

Regulatory framework defining the practical arrangements;

Technical framework: applicable guidelines

Application of these provisions:

Operational procedures for implementation;

Appropriate interpretation of the requirements:

Competence of the personnel;

Capacity development, training, etc.


Conclusions

Regulatory capacity building, promotion of collaboration, convergence and harmonization will continue to be one of the WHO priorities;

Harmonization means nothing if the established common guidelines are not implemented.

There is no good regulation without Good Governance (accountability, transparency, fair and equal treatment of all regulated parties etc.);

Making medicines is no longer a "local" business and the era of locally operating regulators is coming to an end

Dr Gabriela Zenhäusern | Technical officer | RSS | HQ Geneva

Gabriela Zenhäusern, PhD

Technical officer, RHT/RSS/RNH

[email protected]

WHO HQ Geneva

Thank you

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