1 Department of Essential Medicines and Pharmaceutical Policies Introduction to Medicines Quality Assurance and Safety Dr Lembit Rägo Coordinator Quality

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Department of Essential Medicines and Pharmaceutical Policies

Introduction to Medicines Quality Assurance and Safety

Dr Lembit RägoCoordinator

Quality Assurance and Safety: MedicinesEssential Medicines and Pharmacutical Policies

World Health OrganizationGeneva, Switzerland

E-mail: [email protected]

Technical Briefing Seminar, 29 October to 2 November 2012

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Why medicines are special category of products?

Consumers, patients and health care workers have limited capacity to judge there

SAFETY QUALITY EFFICACY

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SmellAppearance Taste

Usual perceptions may not help in Making judgements about medicines …

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Are all medicines safe, effective and meet quality criteria?

No, they are not

Some are safe, but not effective or necessarily meet the quality criteria

Some may be effective, meet quality criteria but are not safe

Some meet quality criteria but are not necessarily safe or have any efficacy

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Quality - Safety

Some safety parameters are determined by quality

Some safety parameters are determined by the intrinsic properties of active pharmaceutical ingredient(s)

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What type of medicines we have?

Originator products Multisource (generic) products

KEY – INTERCHANGEABILITY, more important THERAPEUTIC INTERCHNGEABILITY

ALL LITERATURE IS BASED ON ORGINATORS No interchangeability – NEED FOR NEW SAFETY and

EFFICACY DATA, NEW BOOKS HAVE TO BE WRITTEN

Other type of products Biological products including vaccines and blood products "Biosimilars" Radiopharmaceuticals Traditional medicines

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What type of regulations exist and how they differ?

For innovator products proof of QUALITY, SAFETY and EFFICACY is needed

For multisource products QUALITY, safety and efficacy data is referred to the originator providing only evidence about interchangeability (bioequivalence, clinical testing, in limited cases dissolution data)

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Regulations: Global vs National

National regulations still differ a lot

What is ICH and what it is not?

Regional harmonization initiatives

Do global norms exist for generics?

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In book: Drug Benefits and Risks, Chapter 6, 2008

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Main regulatory functions

Table 1. Principal medicines regulatory functions• Licensing of the manufacture, import, export, distribution,promotion and advertising of medicines• Assessing the safety, efficacy and quality of medicines,and issuing marketing authorization for individualproducts• Inspecting and surveillance of manufacturers, importers,wholesalers and dispensers of medicines• Controlling and monitoring the quality of medicineson the market• Controlling promotion and advertising of medicines• Monitoring safety of marketed medicines includingcollecting and analysing adverse reaction reports• Providing independent information on medicines toprofessionals and the public

Source: WHO Policy Perspectives on Medicines no 7, 2003.

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Is quality of medicines a problem?

Yes, a HUGE problem- 2012 Pakistan case – 135 deaths

- Sri Lanka case – 1 dead, 8 life threatening ADRs

If we would have the same compliance with norms and quality in aircraft industry Globally approximately 25% planes would not take off the grounds 10% would crash and kill the people (treatment failure = killing in some cases; toxicity etc. )

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Quality can not be assessed, tested or inspected into the product, BUT

It has to be built into it!!

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Shifting the regulatory paradigm during the history (1)

From elementary quality requirements to safety and efficacy

From quality control of finished product to control of quality of manufacturing (inspection)

From quality control of finished product and inspection of manufacturing sites in general to more understanding the processes and product specific processes involved

From rigid limits to agreed upon beforehand set of limits which can be used by manufacturers in a more flexible manner

…..

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Shifting the regulatory paradigm during the history (2)

Increased role of science – new molecules, new advanced therapies and combination therapies (device + medicine, etc)

From national to international – not a single regulator today can work meaningfully in isolation and not using other regulators experience/knowledge/information

Increasing need to decide what regulatory functions to fulfil nationally and what expertise/capacities to build nationally

Increasing need for harmonization, collaboration and cooperation The future in medicines regulation is in effective collaboration

and cooperation

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Science and medicines regulation (example): European Medicines Agency (EMA) - First Scientific Workshop On Nanomedicines, 2-3 September 2010, London

Emerging therapies such as nonomedicines give rise to questions on the appropriateness of current regulatory frameworks, the relevance and adequacy of existing requirements and guidelines, and on the availability of adequate expertise to regulators.

Scientific challenges arise from the limitations of current testing methods and the reliability of novel ones, because of the 'nanosize' and the unique behaviour of such nano-systems in biological structures.

Examples of approved nonomedicines: the anti-neoplastic agent Caelyx includes stealth liposomes of doxorubicine

hydrochloride; the antineoplastic agent Mepact contains mifamurtide in multilamellar liposomes; the antineoplastic agent Abraxane contains paclitaxel nanoparticles bound to human

serum albumin; the immunosuppressant Rapamune contains sirolimus particles in nanocrystal

colloidal dispersion.

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Medicines work in WHO HQ – in new Health Systems and Innovation (HIS) cluster. ADG Dr Marie-Paule Kieny

Department of Essential Medicines and Health Products (EMP) Quality Assurance and Safety: Medicines (QSM)

Collaboration with ROs and COs, other clusters/departments/units and CCs

Regional Offices Country Offices Disease oriented programs (HIV/AIDS, TB, Malaria etc.) Other programs … WHO Collaborating Centres

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What is QSM? Seven technical programmes

Regulatory Support International Nonproprietary Names (INNs) Quality Assurance Anticounterfeiting Safety (Pharmacovigilance) Prequalification of Medicines Quality Assurance and Safety of Blood

Products and Related Biologicals

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More information: www.who.int/medicines/en/

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http://www.who.int/medicines/areas/quality_safety/safety_efficacy/en/index.html

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Increasing regulatory transparency

* Claire Cornips, Lembit Rägo, Samvel Azatyan, Richard Laing. International Journal of Risk & Safety in Medicine 22 (2010) 77–88

*

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Active collaboration with other international, regional and national organizations UN family & international organizations:

UNICEF, UNFPA, UNIDO, UNDP etc. MSF

Regional Council of Europe/EDQM EMA/EU NEPAD

Professional and scientific FIP, IUPHAR, ISPE

National NMRAs

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WHO collaborating centres (CCs) for medicines

Historically initiated both by regions and the HQ More regional focus of activities More Global focus of activities

WHO CCs linked to medicines Parts of various institutions, mostly universities but also Government

institutions including regulators Independent organizations, units with only CCs objectives

WHO CCs by profiles CCs linked to overall medicines related topics and not necessarily linked to

medicines regulation Medicines policies & research, rational use of medicines, drug utilization

research, assessment for reimbursement & other purposes, pricing etc. CCs linked to various functional parts of medicines regulation including

nomenclatures, classifications and dictionaries Nomenclatures, dictionaries, methodologies, quality control, pharmacovigilance,

research etc.

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Nomenclatures and classifications

WHO Collaborating Centre for Drug Statistics Methodology Director / Head: MScPharm Hanne Strøm; [email protected]: Department of Pharmacoepidemiology Norwegian Institute of Public Health. Address: Marcus Thranesgt 6, PB 4404 Nydalen 0403, Oslo, Norway. Web Site: http://www.whocc.no

Terms of Reference: To classify drugs according to the ATC system. To establish DDDs for drugs which have been assigned an ATC code. To review and revise as necessary the ATC classification system and DDDs. To stimulate and influence the practical use of the ATC system by cooperating

with researchers in the drug utilization field. To organize training courses in the ATC/DDD methodology and to lecture

such courses and seminars organized by others. To provide technical support to countries in setting up their national medicines

classification systems and build capacity in the use of medicines consumption

information.

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Pharmacovigilance

Title of the centre: WHO Collaborating Centre for International Drug MonitoringDirector / Head: Professor Marie Lindquist, [email protected]@who-umc.org Institution: The Uppsala Monitoring Centre – known as UMC

Address: Box 1051, S-751 40, Uppsala, Sweden

Web Site: http://www.who-umc.org Terms of Reference: Collection & processing of data: maintaining &

developing the international adverse drug reaction database currently containing 7 million + cases of suspected drug reactions from over 100 countries.

Data utilization: a) Regular screening of data & distribution of feed-back as determined by the collaborating centres; b) With the help of expert consultants , evaluate new data & produce & distribute "Signal" which alerts on new adverse issues; c) Special database searches on request from both within & outside the Programme.

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Pharmacovigilance

WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance. Director / Head: Dr Alexander Dodoo

Institution: Centre for Tropical Clinical Pharmacology & Therapeutics University of Ghana Medical School, P. O. Box 4236 GP, Greater Accra

Terms of Reference: Training in pharmacovigilance in African countries for building and strengthening of spontaneous adverse drug reaction reporting systems

Advocacy for pharmacovigilance across Africa either alone or in collaboration with WHO Promoting the integration of pharmacovigilance into public health programmes Technical support to national pharnacovigilance centres Support in communication and crisis management to national pharmacovigilance centres Acquisition (from WHO, UMC) and distribution of needed literature and technical tools to national

pharmacovigilance centres and governments Research in pharmacovigilance including cohort event monitoring of specified medicines Assistance in the development and maintenance of pregnancy registers

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4.2. Quality control (WPRO, SEARO, AFRO – 4)

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Department of Essential Medicines and Pharmaceutical Policies 2

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15th ICDRA – www.icdra.ee

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Documents

1 Department of Essential Medicines and Pharmaceutical Policies Introduction to Medicines Quality Assurance and Safety Dr Lembit Rägo Coordinator Quality