Medicines Theme Days

Medicines theme Days

Brussels

September 21-23 2010

Report

1  Introduction

The AEDES Foundation organised the theme days dedicated to medicines on the 21-22-23 September 2010 in Brussels.

This conference brought about fifty participants together, from many different points of view within the medicines sector.

-  AEDES technical staff;

-  Experts related to AEDES, to other organisations from civil society, working in specialised fields relating to medicines, pharmaceutical manufacture, quality assurance, medicines supply chain management, pharmaceutical regulation, health economics and public health;

-  Professionals specialising in medicines working in several international organisations: WHO, Global Fund, Roll Back Malaria, and Affordable Medicines Facility - Malaria.

-  Representatives of European and African supply structures, both from the public and private sectors: ACAME, CAMEG (national authority of Burkina Faso), Saphar (private wholesaler, Niger), CSEP (international private procurement agency), SMI (idem);

-  Representatives of pharmaceuticals regulatory authorities: AFMPS (Belgian Medicine Authority), OCEAC (Central African regional organisation);

-  Representatives from various networks: OTECI, ReMeD, QUAMED, ATM Index, Because Health;

-  Representatives from various academic institutions: IMT, University of Ghent, PHA;

-  Representatives from civil society: OTECI, MSF, Fondation Mérieux, Africa Europe Faith and Justice Network

The purpose of the theme days was to bring together professionals dealing with medicines in order to draw up a report on interventions in the field of medicines, and in particular with respect to the quality aspects of medicines.

The report was envisaged as wide ranging, covering 3 major axes:

(i)  The axis « Knowledge of the market in medicines with respect to production sources and intrinsic quality of medicines »;

(ii)  The axis « The supply chain (purchase / distribution), with respect to how it is organised and the actors involved (private and public sector) »; and

(iii)  The axis «Regulation of the medicines sector via the framework of pharmaceuticals regulation».

The days proceeded as we wished, acting as a genuine platform for communication, allowing all delegates to express their points of view and to bring their own experience and the fruits of their own thinking to bear on the subjects treated, with the aim of contributing to collective reflection on needed interventions in the sector and of developing coherent strategies in the field of medicines, for the benefit of all participants and, by extension, for the populations concerned.

Each of the days, devoted to a particular axis, was organised as follows:

-  A brief introduction, presented by the moderator for the day, gave a description of present thinking on the question and the main questions to be posed.

-  Each broader subject was divided into several narrower subdivisions, helping to structure the field.

-  The mornings were devoted to a series of presentations, given by various representatives invited, on the particular subjects proposed.

-  Afternoons were devoted to group discussions, centred on the particular themes of the day. Each group was guided by a series of concrete questions relating to the particular subject, the aim being to develop systematically pragmatic ideas and suggestions for further work on the subjects treated.

-  At the end of each day, the results of the group discussions were explained and discussed in plenary session.

Why did AEDES take the initiative to organise this conference?

For a number of years, the AEDES Foundation has been encouraging reflection upon the problems of medicines in low and middle income countries, as well as carrying out research on the problem.

In particular, it has conducted research which led to publications on drug dumping, in the context of gifts of medicine..

It participates in projects for improving access to effective and quality treatments for malaria (report on needs for ACT derivatives in 4 African countries, identification and application of the Artepal project, participation in the carrying out of the A2S2 project).

More generally, the Foundation is concerned with concrete questions relating to the quality of essential medicines in countries where pharmaceutical regulation is weak.

2  Summary of proceedings

Day 1 - Axis 1

« Knowing and understanding the pharmaceuticals market from the Production source and Quality point of view »

Theme for the day

Day 1 of the Medicine Theme Days was devoted to knowledge and understanding of the market in medicines with respect to « production sources » and « quality ».

This general theme was subdivided into three specific subjects:

-  Subject 1: Knowledge, assessment and promotion of local production of MEGs

-  Subject 2: Assessment and selection mechanisms for international MEG sources

-  Subject 3: International Institutions and Political Initiatives: What impact on accessing quality MEGs?

The results of Day 1 can be summarised as follows:

Knowledge, assessment and promotion of local production of MEGs

Firstly, we should clarify what is understood by the terms « local production » of MEGs: we understand by this term manufacturers in low and middle income countries whose production is used strictly within the structure of the local (national) market. Manufacturers of this type have been audited, for example, by FEDECAME. Generally, the standards applicable to « local manufacturers » are and should be identical to the standards applicable to international manufacturers. On the other hand, with the aim of supporting important existing production, decisions at the local level may be taken not to exclude certain manufacturers / products if the manufacturer commits itself to complying with those standards and if monitoring or support are possible in practice. This type of conditional licensing combined with monitoring is much more difficult to apply at the international level.

The reflections which follow apply both to the local market (when speaking, for example, of support for the development of « local manufacturers ») and to all manufacturers, whether local or international (in particular when referring to basic principles and applicable standards).

Because of the weaknesses of National Pharmaceutical Regulatory Authorities in the majority of low and middle income countries in terms of technical capacities and financial resources, as well as wide differences in levels of inspection from one country to another, the principle of GMP audits of producers, both local and international, is relevant and must be continued and even strengthened.

The carrying out of such audits must however be rationalised and improved. For this purpose, several proposals were made:

-  Rationalisation of audit procedures:

Currently, each purchasing organisation which has included the GMP audit in its qualification procedure for MEG acquisition sources carries out its own audit, independently of other organisations. This sometimes leads to needless and burdensome duplication for producers, with consequences which can be negative: cost, lack of alertness when faced with repeating procedures for the same type of market, etc. Coordination between the auditing organisations, as well as regrouping themselves on the same platform, including the principle of data exchange (see below).

-  Setting up milestones leading to mutual recognition:

Qualification for suppliers (i.e., manufacturers or distributors) must be carried out on the basis of a common frame of reference (GMP or GDP). The latter exists and has been drawn up by the World Health Organisation: several successive versions can be found in WHO technical reports, available on line. These frames of reference must be divided into a series of observations ranked by degrees of criticality (« critical », «major», «minor» observations), which is normally done by auditors in a subjective fashion for there is no current official harmonised ranking. Finally, the expertise of assessors needs to be mutually recognised, for example by setting up an accreditation system for auditors and by organising standardised training for auditing.

-  Pooling and exchange of data:

In order to avoid duplication of work, pooling is necessary, facilitated by acceptance of a common frame of reference and updating of skills. The idea of a database which could be shared by auditors was suggested during the discussions. In order to prioritise efforts, certain molecules thought to be of priority status should be targeted (i.e., second line TB drugs, penicillin and some major antibiotics, paediatric formulations, etc.).

-  Strengthening technical capacities:

Involvement of local actors (pharmaceutical regulatory authorities, industrialists) must always be considered. The audit should include steps for training and supporting « local manufacturers » (in the sense defined in the Introduction) in a step by step attempt at improvement. The application of recommendations often requires outside expertise. A flying team made up of national and international experts could carry out this type of support.

-  Prior economic and financial requisites:

Audits and above all the support missions for bringing production factories up to standard are substantial investments. Prior steps are therefore required before they can be applied: these procedures should be targeted in the most positive and constructive manner possible, in other words, it is necessary to ensure that the factories singled out for attention should have genuine economic potential; local production must aid access to essential quality medicines at suitable prices, which implies that the manufacturing organisation must be profitable and viable over the long term. Currently, work in this area has been carried out by UNIDO: this organisation works to support production structures in low and middle income countries, for carrying out business plans for factories. At the present time this work is essentially economic and financial. In time it could / should also develop a technical approach.

Nevertheless, audits, although helping to provide technical assistance for bringing manufacturers up to date, do not have the power to enforce change. Self-enforcing systems which influence the Market have been initiated in some programmes (WHO/PQ, AMFm) and are thus additional methods complementing audit procedures, helping to increase their impact and to make them genuinely useful.

Assessment and selection mechanisms for international MEG sources

The mechanism and methodology for assessment proposed by FEDECAME (Democratic Republic of the Congo) are representative of the manner in which this procedure has been approached by procurement structures in low and middle income countries. The procedure should be widened to cover all purchasing structures (CAME...) for multi-source medicines.

It seems clear that, in the world of French speaking African CAME in general, the qualification procedure for supply sources has been developed by replacing the assessment mechanisms for medicines by registration by National Pharmaceutical Regulatory Authorities, which are frequently lacking or insufficient at the technical level.

On the other hand, the documentation requested from suppliers for pre qualification on the one hand and for the registration request on the other, although not identical, are very close with regard to content. From the point of view of the manufacturer they duplicate the work involved, entailing significant costs. From the point of view of the analysis required, this duplicates the procedures, with all its consequences in terms of mobilising the necessary human resources and skills, which are often lacking in low and middle income countries.

Cooperation between the purchasing authorities and the National Pharmaceutical Regulatory Authorities in the search for a shared procedure for qualifying sources at the level of the authorities and for registering MEGs authorising their entry on the public market (i.e., public services) would be very welcome. Systematisation of the links between CAME and the NRA, formally involving the latter in the procedure for qualifying sources of CAMEs, is proposed. In countries where registration procedures are not very highly developed and NRAs are particularly weak in terms of human resources and skills in this particular field , their involvement in the processes for qualifying sources carried out by the purchasing authority should help to progressively develop assessment mechanisms for registering MEGs.

Action at the level of national and international institutions

The donors have the power to influence the market at the international level, as shown by the influence of the Global Fund quality assurance policy on the production of antiretrovirals (ARV). Harmonisation of QA policies at the donor level is necessary and would help to strengthen that influence, with positive results in quality terms.

The National Pharmaceutical Regulatory Authorities remain key actors. More involvement by the NRAs in the source selection process is required, which necessitates strengthening their technical and financial capacities, which in turn necessitates a reorientation of resources. In effect, the donors generally finance activities which have visible and immediate results; the strengthening of the NRAs is on the contrary a long term process, needing a strategy covering several years.

The success of the WHO Pre Qualification Programme is currently limited to three large scale global pandemics and to the main molecules directly used for their treatment: ARV , first line anti TB drugs, ACT. The extension of the WHO/PQ programme to other products (i.e., penicillins and other antibiotics, certain particularly active medicines, etc.) but also to other actors remains to be accomplished. The involvement of sub regional groups in the Programme would help to strengthen a reinforcement in capacities, the re establishment of the roles and responsibilities of regional actors (NRAs) and a better division of the work load between a larger number of actors.

Day 2 - Axis 2

« The Supply Chain (Purchasing and distribution) »

Theme for the day

Day 2 of the Medicines Theme Days was devoted to the « supply chain (procurement and distribution) »

This general theme was subdivided into three specific subjects:

-  Subject 1: Financial mechanisms for improving access to MEGs

-  Subject 2: Organization of MEG supply networks

-  Subject 3: Operational approaches public / private sectors

The results of Day 2 can be summarised as follows:

New mechanisms for health financing

Mechanisms for financing health are currently in a state of change. Mechanisms essentially based upon financing the input necessary for the development of services are giving way to mechanisms based on the use of the services and results. As far as medicines are concerned, these new mechanisms clearly have (or will eventually have) major implications for financing methods for this particular input and for the development of the « market » in low and middle income countries: health system actors will have a much more active and important role in the choice of their own sources of supply, in a market which will have to be regulated and where the traditional public sources (purchasing authorities) may well find themselves increasingly in competition with licensed actors in the private sector.