1 |1 | who technical briefing seminar on essential medicines and health products, 3-7 november 2014,...

1 |WHO Technical Briefing Seminar on Essential Medicines and Health Products,3-7 November 2014, WHO Headquarters, Geneva

Dr Samvel AzatyanGroup LeadCapacity Building and Harmonization SupportRegulatory Systems Strengthening [RSS]Regulation of Medicines and Other Health Technologies [RHT]Department of Essential Medicines and Health Products [EMP]World Health OrganizationE-mail: [email protected]

Capacity building and technical assistance to regulators; Regulatory cooperation and harmonization initiatives

mailto:[email protected]


Why regulating medicines (1)

In most cases, consumers are not in a position to make decisions about when to use medicines, which medicines to use, how to use them and to weigh potential benefits against risks as, by definition, no medicine is completely safe.

Even healthcare professionals (medical doctors, pharmacists) sometimes have difficulties to take informed decisions about all aspects of medicines, unless they are specially trained.


Why regulating medicines (2)

Consequences of the use of ineffective, poor quality, harmful medicines, public health and safety concerns have obliged governments to intervene in the activities of the pharmaceutical sector by establishing medical products regulation;

In this context, medical products regulation is a public policy that restricts private sector activities in order to attain social goals set by the Government.


The overall objective of a National Regulatory Authorities (NRAs) for medical products is to ensure that all medical products (medicines, vaccines, blood products and other biologicals, traditional medicines and medical devices) that are used in a country are of assured quality, safety and efficacy and are accompanied by appropriate information to promote their rational use.

To fulfill this task NRAs need to be competent, capable, independent, with strong political back-up and to have clear authority to enforce established regulations.

The role of National Regulatory AuthoritiesThe role of National Regulatory Authorities


Where we are with national regulatorysystems today (1)


≈30% of NMRAs globally have limited capacity to perform all core regulatory functions

≈90% of African NMRAs lack capacity to guarantee quality, safety, and efficacy

Manufacturers / applicants face a landscape of disparate regulations, frequent delays, and limited transparency

As a result, needed medicines lack availability, affordability in low-and middle income countries Fewer medicines are available in low-income countries than in the

US, EU and other well-regulated markets. Cost of inefficient regulatory systems drives up medicines prices.


Some summary observations: Guidelines and assessment procedures are not

up to international standards and are often of an administrative rather than technical nature;

Wide-ranging exemption clauses exist which are not justified by a risk assessment, for example for public sector imports or donations;

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 Prequalification Programme), or by other competent authorities.



26 country study in Africa


What WHO is doing to support regulators (1)What WHO is doing to support regulators (1)

1. Developing evidence, maintaining knowledge and understanding of situation and needs of regulatory systems worldwide. This is done by:– proactively seeking information on national level, including

assessing national regulatory systems upon request from Member States

– Internationally, by participation and contribution in regional and sub-regional regulatory networks:• International Conference on Harmonization (ICH);• Asia-Pacific Economic Cooperation Regulatory

Harmonization Steering Committee (APEC RHSC);• Organization of Islamic Cooperation;• African Medicines Regulatory Harmonization Initiative

(AMRH).

http://www.ich.org/



2. Based on assessed needs, providing direct country support through technical advice, trainings, seminars, and other specific capacity-building activities – in accordance with the Institutional Development Plans (IDPs).

3. Developing and continuously improving tools to assist regulatory work (e.g. standards, guidelines, manuals, databases and other information materials, as well as tools for exchange of regulatory information):– Implementation of WHO Certification scheme on

the quality of pharmaceutical products moving in international commerce - update and expansion to include starting materials



4. Providing direct support to regional/sub-regional networks through technical advice, training, seminars, and other specific capacity-building activities including establishing subregional/regional centres of excellence and training networks (e.g. through Technical Working Group on Regulatory Capacity Development in Africa).

5. Organizing representation in regional and global regulatory initiatives and facilitating dissemination of information through different relevant platforms.

6. Promoting WHO’s regulatory strengthening work and its output to ensure visibility and accessibility to interested regulatory counterparts: http://apps.who.int/prequal/ .

http://apps.who.int/prequal/

http://apps.who.int/prequal/

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WHO Technical Briefing Seminar on Essential Medicines and Health Products,3-7 November 2014, WHO Headquarters, Geneva

Map of training activities by area of work and type of training

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Developing evidence:—Assessments of national regulatory systems conducted in

Democratic Republic of Congo (DRC), Kenya and Zambia in 2014;

Providing direct technical support to Regional Economic Communities (REC):

—Training provided in March 2014 to UEMOA countries on Common Technical Documentation (CTD) and on technical, scientific and administrative guidelines for registration of generic products;

ACP – African, Caribbean and Pacific.

WHO/RSS activities in supporting ACP regulators (1)


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Providing direct technical support Countries:

—Training provided in July 2014 on Good Manufacturing Practices (GMP): Field work through on-site visit of local manufacturer in DRC;

—Technical advice provided to countries on ad-hoc basis on the broad spectrum of pharmaceutical regulation

Promoting WHO Norms and standards:

—Development of the revised version of the WHO/RSS Regulatory Technical Package containing relevant guidance for regulators.



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Regulatory Capacity Building for Influenza Vaccines inGlobal Action Plan (GAP) Countries

Regulatory Capacity Building for Influenza Vaccines inGlobal Action Plan (GAP) Countries

Regulatory Function

Activity 2006-2014 Participants

Marketing Authorization

• Training on quality assessment of influenza vaccines, 2013, USA 6 countries

Lot release & lab access

• QC training, 2008-2012, NIBSC, UK• QC training and manufacturing, 2008-2010, NVI, Netherlands• Participation in international proficiency study, 2012-2014, GAP

countries

30 regulators 10 regulators 22 NRAs and

manufacturers

Regulatory Inspections

• GMP inspection training, 2011, Rep. S. Korea • Fundamentals of GMP Influenza Vaccine Manufacturing, 2013, USA• Regulatory Inspection Risk Approach, 2013, Brazil

36 regulators

Clinical trials • Clinical trial design for combination & influenza vaccines workshop, 2008, Switzerland

• GCP inspection training, 2011, S. Africa• Regulatory requirements for the preclinical/non-clinical and clinical

evaluation of influenza vaccines workshop, 2014, Thailand

40+ regulators and

manufacturers

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International Conference of Drug Regulatory Authorities (ICDRA)

International Conference of Drug Regulatory Authorities (ICDRA)

The ICDRA conferences have been held biannually since 1980 with the aim of promoting exchange of regulatory information on medical products and collaborative approaches to issues of common concern;

ICDRA is a platform established to develop international consensus on regulatory matters;

After 30 years of existence ICDRA continues to be an important tool for WHO and medicines regulatory authorities in their efforts to harmonize regulation and improve the safety, efficacy and quality of medicines.

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Over the past thirty years, the main objectives of the ICDRAs have remained almost unaltered:

Over the past thirty years, the main objectives of the ICDRAs have remained almost unaltered:

to promote collaboration between national medicines regulatory authorities. to reach a consensus on the matters of common interest. to facilitate timely and adequate exchange of information. to discuss issues of international relevance.

1st 1980 Annapolis (USA)2nd 1982 Rome (Italy)3rd 1984 Saltsjobaden (Sweden)4th 1986 Tokyo (Japan)5th 1989 Paris (France)6th 1991 Ottawa (Canada)7th 1994 Nordwijkerhout (Netherlands)8th 1996 Manama (Bahrain)

9th 1999 Berlin (Germany)10th 2002 Hong Kong (S.A.R. China)11th 2004 Madrid (Spain)12th 2006 Seoul (Republic of Korea)13th 2008 Bern (Switzerland)14th 2010 Singapore15th 2012 Tallinn (Estonia)16th 2014 Rio de Janeiro (Brazil)

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ICDRA is the regulators' "voice"ICDRA is the regulators' "voice"

In collaboration with the host country WHO is contributing in organization of ICDRA conferences: Planning; Development of the conference programme; Liaison with the host country's NMRA; Validation and approval of registrations; Supporting participation of developing

countries' regulators; Organization of side meetings/events; Technical and logistic support during the event; Collation and preparation of the

recommendations.

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What is regulatory harmonization?What is regulatory harmonization?

In a broad sense harmonization means harmonization of technical requirements for medicines regulation, i.e., legislations, guidelines, procedures, etc.

Different types of the guidelines and other normative documents are available for regulators: National (Individual counties); Regional (e.g., EU, ASEAN, PANDRH, EAC, SADC, UEMOA,

WAHO, etc.); International (WHO, ICH, PIC/s).WHO guidelines (international) are available on most ofthe technical requirements for generic medicines

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Why regulatory requirements need to be harmonized?

Why regulatory requirements need to be harmonized?

Current (not harmonized) environment Harmonized environment

Individual National Medicines Regulatory Authorities (NMRAs) governing medical products registration

Paperwork, technical requirements, and other registration steps differ across NMRAs

Manufacturers must invest significant time and effort in each registration, so a limited set of countries are targeted

No clear timelines for a drug to clear registration and be ready for the market

Little transparency before or during the process

Regional economic communities (RECs) and other country groupings covering the entire world

Common documentation, procedure, and decision-making framework across all RECs

Low cost to register in each additional country, so coverage is more broad and equitable

Streamlined process that is faster and easier

Clear understanding of the process by all parties involved

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Identification of technical documentsfor harmonization

Identification of technical documentsfor harmonization

No need to invent a bicycle.. When appropriate guidelines exist elsewhere it

is not necessary to develop new documents from scratch;

The simplest and most cost-effective way is to adopt the content and format of already existing guidelines, with, if necessary, modifications to accommodate the local situation.

True harmonization is not just developmentof common documentation - MOST EFFORTS SHOULD GO FOR THE IMPLEMENTATION!

PIC(s)

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African Medicines Registration Harmonization Initiative (AMRH) – Consortium of partners

African Medicines Registration Harmonization Initiative (AMRH) – Consortium of partners

The overall objective of this initiative is to achieve a harmonized medicines registration process in countries belonging to the Regional Economic Communities (RECs), based on common documents, processes and shared information systems at the level of RECs.

WHO's main role in this initiative is: To provide technical assistance in development and implementation of

harmonized approaches for registration of medicines; • Support Technical Working Groups in 4 areas: Medicines Evaluation

and Registration, Good Manufacturing Practices (GMP), Information management systems (IMS) and Quality Management Systems (QMS);

Support regulatory capacity building, training and joint activities.• Chairing the Technical Working Group on Regulatory Capacity

Development in Africa.

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Main objective – To facilitate harmonization, sharing of expertise and trust building.

EAC MRH specific objectives - establishment of a framework for:– Joint reviews and inspections of manufacturing sites;– Marketing authorization by EAC NMRAs.

1st joint assessment series: 2010 – 2011– Two products – Abacavir Sulphate tablets 60mg and Amikacin injection;– Outcome - Jointly accepted in January, 2011;– Countries’ approval took place after 3 – 7 months from the date of joint

acceptance by EAC/WHO.

Joint WHO/EAC assessment sessions (1)Joint WHO/EAC assessment sessions (1)

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2nd joint assessment series (TFDA data)– 4 sessions from July 2013 to April 2014.

No Reference number Product name Common name and strength

Date received by WHO

Date received by TFDA

Date of joint acceptance by WHO/EAC

Date of registration by TFDA

1TFDA13/HM/0261 (WHO PQP No. RH039)

Misoprost 200 Misoprostol 200μg 26/3/2013 26/6/2013 8th April 2014 5th May 2014

2TFDA13/HM/0262 (WHO PQP No. RH040)

Pill 72 Levonorgestrel 0.75mg

1/5/2013 26/6/2013 8th April 2014 5th May 2014

3TFDA13/HM/0290 WHO PQP No. MAL101

Falcimon 25/67.5

Artesunate 25mg + Amodiaquine 67.5mg

27/3/2013 16/7/2013 8th April 2014 5th May 2014

4TFDA13/HM/0291 (WHO PQP No. MAL102)

Falcimon 100/270

Artesunate 100mg + Amodiaquine 270mg

27/3/2013 16/7/2013 8th April 2014 5th May 2014

5TFDA13/HM/0292 (WHO PQP No. MAL103)

Falcimon 50/135

Artesunate 50mg + Amodiaquine 135mg

27/3/2013 16/7/2013 8th April 2014 5th May 2014

Joint WHO/EAC assessment sessions (2)Joint WHO/EAC assessment sessions (2)

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Lessons learnt from joint activitiesLessons learnt from joint activities

Capacity (knowledge and skills) built for EAC Partner States NMRAs experts;

Quicker access of prequalified and jointly accepted medicines - Reduced timelines for registration ;

NMRAs scarce resources saved – No duplication of work; Used as a platform for trust building among EAC regulatory

experts; Lays foundation for better cooperation among EAC NMRAs –

potential for future mutual recognition of regulatory decisions among EAC Partner States NMRAs.

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ConclusionsConclusions

Medical products regulation is not anymore a "single-player" activity;

Harmonization of regulatory requirements, work sharing and collaboration can help reduce workload and improve public health by improving overall regulatory performance.

It can help to direct the expert knowledge and resources to performance of the functions that can improve public health and facilitate access to essential medicines;

Formation of effective networks between regulatory authorities nationally and internationally may facilitate sharing of scarce resources and eliminate duplicating of activities.

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Thank you!www.who.int/medicines

Graphic: www.eauc.org

http://www.who.int/medicines

http://www.eauc.org/

1 |1 | who technical briefing seminar on essential medicines and health products, 3-7 november 2014,...

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