1.1 Background

Antiretroviral therapy, prevention and treatment of opportunistic infections and cancers, as well as palliative care are important elements of HIV/AIDS care and support. HIV/AIDS care hence requires a wide range of essential medicines. If available, these effective and often relatively inexpensive medicines can prevent, treat, or help manage HIV/AIDS and most of the common HIV-related diseases.

Less than 8% of people who require antiretroviral (ARV) treatment can access these medicines in developing countries (see Figure 1).

The high price of many of the HIV-related medicines and diagnostics offered by common suppliers - especially antiretroviral and anti-cancer medicines - is one of the main barriers to their availability in developing countries.

There are several other important barriers, including a lack of the basic components required for care, treatment, and support of people living with HIV/AIDS (PLWA) such as: trained staff in health facilities, constant availability of laboratory equipment and supplies, sufficient funding, efficient pharmaceutical services, strong political will and government commitment. Wider availability of information on prices and reliable sources of medicines can help those responsible for procurement make better decisions.

Since 2000, prices of important first-line ARVs have fallen considerably. This trend is attributable to a cumulation of factors including advocacy, corporate responsiveness, competition from generic manufacturers, sustained public pressure, and the growing political attention paid to the AIDS epidemic. In addition, originator companies began announcing discount offers for the benefit of the poorest countries or those where HIV/AIDS prevalence is highest⁷.

⁷ HIV prevalence status of countries see www.who.int/emc-hiv/fact_sheets/All_countries.html

Furthermore, the announcement of WHO’s “3 by 5” initiative of providing ARV treatment to 3 million PLWA in developing countries by the end of 2005 has lead to anticipation that increased volumes of medicine will be purchased. This may further reduce the prices of certain medicines.

Treating 3 million people by the end of 2005 will require concerted, sustained action by many partners. To chart the direction and to show what WHO itself will be doing to accelerate action, WHO has developed an initial strategic framework. WHO’s 3 by 5 team assembled and refined the framework in intensive consultation with partners. This consultation will continue, and the framework itself will continue to evolve.

WHO’s strategic framework for emergency scaling up of antiretroviral therapy contains 14 key strategic elements. These elements fall into five categories - the pillars of the 3 by 5 campaign:

1. Global leadership, strong partnership and advocacy
2. Urgent, sustained country support
3. Simplified, standardized tools for delivering antiretroviral therapy
4. Effective, reliable supply of medicines and diagnostics
5. Rapidly identifying and reapplying new knowledge and successes

The full text of the WHO strategic framework can be found at: http://webitpreview.who.int/entity/3by5/publications/documents/en/3by5StrategyMakingItHappen.pdf

In addition, drug users, PLWA and their advocates from around the world have urged WHO to ensure the inclusion of injecting drug users in the scale-up of ARV therapy in its 3 by 5 initiative (Media Alert dated 19 February 2004).

The new simplified ARV therapy guidelines mentioned in the 3^rd pillar also allow for cost savings and real scaling-up activities through the potential use of cheaper fixed-dose combinations (FDCs), where countries are favorable to import generics or where local production facilities exist⁸.

⁸ More information on fixed dose combinations can be obtained from the MSF briefing note: Two pills a day saving lives: Fixed-dose combinations (FDCs) of antiretroviral drugs, MSF, Feb 2004 (see http://www.accessmed-msf.org/documents/factsheetfdc.pdf)

Figure 1. Estimated percentage of people covered among those in need of antiretroviral treatment, situation as of November 2003

Source: WHO/UNAIDS. Treating 3 million by 2005 - Making it happen. Geneva, WHO, 2003.

1.2 Aim

This report sets out to provide market information that can be used to help procurement agencies make informed decisions on the sources of medicines and diagnostics, and serve as the basis for negotiating affordable prices. The aim is to help increase access to treatment for PLWA in developing countries.

The data provided by the manufacturers serve to draw attention to the multiplicity of suppliers and the variation in price of some essential HIV/AIDS-related medicines on the international market. Without this information, there is a risk that low-income countries may be paying more than needed to obtain HIV/AIDS-related medicines. Price variations are highlighted through the tables and graphs included.

However, provision of price information addresses only one barrier to access to medicines in countries with limited resources. It should be noted that many other factors will affect the availability of medicines. Some of the other issues that must be considered are health infrastructure, human resources, funding and supply and distribution systems^9.

⁹ Management Sciences for Health and the World Health Organization second edition of Managing Drug Supply provides a complete overview as well as step-by-step approaches on how to manage pharmaceutical systems effectively.

1.3 Target audience

This report is intended for use primarily by national procurement agencies in resource-limited countries that lack easily accessible information on reliable sources and prices of medicines and diagnostics.

It may also be useful to others involved in the procurement of medicines and diagnostics, such as not-for-profit organizations, distributors, importers and wholesalers or public health professionals interested in current price levels of medicines and diagnostics for PLWA.

Those who will become involved in planning and implementing HIV/AIDS care and treatment interventions will find important regulatory information in this document.

1.4 Generating the report

This is the fifth in a series of annual reports commenced in 1999, investigating sources and prices of medicines and diagnostics commonly required by PLWA, but difficult to obtain locally due to a small number of producers, the lack of distribution channels, or high prices. These surveys will be continued and the report will be regularly updated and made available when appropriate.

A survey was carried out from December 2003 through to January 2004. The responses of 84 manufacturers in 29 different countries as well as those participating in the WHO bulk procurement scheme (see Chapter 2) formed the basis of this report. The number of manufacturers reached has greatly increased since the first survey in 1999 as more resources are made available via industry websites and cooperation with other international organizations. Manufacturers that participated in previous surveys, those held in various databases, and those belonging to National Pharmaceutical Associations were contacted for voluntary participation and for completion of a questionnaire.

The UNAIDS Secretariat, UNICEF, MSF, and WHO have worked jointly to conduct a price survey and put together the results into a comprehensive publication, whilst respecting the manufacturers’ requests for confidentiality with respect to their individual pricing information.

It must be pointed out that the companies included in this report have been screened only through the completeness of the requested documents they have provided, such as the questionnaire, a National GMP certificate, and associated documents relating to the company and their products. Inclusion in this report does not necessarily constitute prequalification or approval of any sort by UNICEF, WHO, UNAIDS or MSF. Only those products identified in Annex 2B in bold and with an asterisk (*) have (at the time of publication of this document) been approved through the ongoing Pre-qualification Project (see Chapter 3).

Additional companies are sought for future updates of this publication.

1.5 Theme of the report: Diagnostics

Increased access to ARV medicines has also highlighted the need for appropriate and cost-effective HIV/AIDS diagnostic support. Diagnostic technologies are important to monitor the progression of the safety and efficacy of treatment, and the development of resistance.

The existing systems for assessment and procurement of HIV test kits is being expanded to include technologies used to monitor ARV therapy (CD4+ counts and viral load) and drug resistance. An overview of types of CD4+ T-cell enumeration technologies available are given in Annex 1A whilst information on HIV viral load technologies is given in Annex 1B.

1.6 How to use this report:

1.6.1 Information on prices

Detailed price information is provided in Chapter 4 and in the MSF document included in Annex 5.

Chapter 4 provides prices of medicines and diagnostic tests based on data obtained from the survey. Official UN exchange rates for the month of February 2004 were used to convert local currencies into US dollars. The prices you will find listed in section 4.1 are provided as statistical ranges explained below.

Price ranges and how these prices are distributed indicate what a purchaser should expect to pay when planning procurement. Section 4.2 provides negotiated prices of essential HIV test kits of the UN bulk procurement scheme 2004.

Annex 5 is a contribution from MSF and is the latest version of their bi-annual publication Untangling the Web of Price Reductions: a pricing guide for the purchase of ARVs for developing countries.

Most of the prices in this report are ex-works (EXW) or Free Carrier (FCA). They do not include added costs such as freight, insurance, import duties or taxes. For this reason the prices in this report cannot be compared with consumer prices. Many countries continue to impose considerable import duties, tariffs and taxes on the price of essential medicines¹⁰. In addition, wholesale and retail mark-ups vary from one country to another. As a result, the EXW price is often less than half end-price to the consumer.

¹⁰ See Policy and programming options for reducing the procurement costs of essential medicines in developing countries, Levinson, L, Boston University School of Public Health, 2003

The following structure is used for reporting the price information:

 

(a) Therapeutic category (according to the WHO Model List of Essential Medicines)

(b) The number of manufacturers that provided an indicative price and the number of countries they represent

(c) The indicative price

(d) The List prices are used to indicate the difference in price, if any, between a developing and a developed country. Brazilian prices are selected as Brazil is a developing country with considerable manufacturing capacity; and Spanish prices because these are generally considered the lowest in Europe.

unit

The price quoted relates to the unit described. For example, if the unit is “tablet” the price quoted is for one single tablet.

max

The maximum price listed represents the highest price among products in this category, with no differentiation between originator or generic products.

min

The minimum price listed represents the lowest price among products in this category, with no differentiation between originator or generic products.

median

The median price is the middle price, or where there is an even number of prices listed, it is the mean of the two middle numbers. This means that half the prices quoted are above this median price, and the other half are below it.

25th perc

The 25^th percentile is the value point representing the first quartile of quoted prices in ascending order. It is used to give some indication of the dispersion of prices for a given product.

For example, if 4 suppliers were identified as manufacturing cefixime paediatric oral suspension, 100 mg/5 ml, and the 25^th percentile is US$ 0.023 per ml of suspension: 1 out of the 4 (a quarter) manufacturers surveyed offer a price equal to or less than US$ 0.023.

Brazilian list price

The Brazilian list price included in this report represents the minimum price payable by Brazilian health institutions, between 01/01/2003 and 01/01/2004, for the product and is taken from the Brazilian databank of health purchases (refer to http://bpreco.saude.gov.br/pls/BPREFD/consulta.inicio). Where the entry reads “none”, this indicates no purchase has been made for that product, therefore no minimum price payable is available.

Spanish list price

This EXW price has been calculated by applying the new margins (as stated in the Royal Decree 286/2001) to the consumer price as published by The General Spanish Council of Pharmacists and Pharmaceutical Associations. (www.portalfarma.com). It should be noted that Spanish list prices are generally considered the lowest in Europe. In most cases, the indicative prices listed in the report are a fraction of the comparative prices in the Spanish list.

1.6.2 Information on sources

Complete lists of manufacturers, their contact information, and the HIV/AIDS-related medicines and diagnostics they manufacture are given in Chapter 5. Annexes 2A and 2B provide a country by country list of the registration status and sources for each of these medicines.

1.6.3 Selection of medicines and diagnostics

This report includes antiretroviral medicines, medicines used to treat a range of opportunistic infections, medicines for use in palliative care, medicines for the treatment of HIV/AIDS-related cancers and medicines for the management of opioid dependence. It also provides information on a range of test kits available for diagnosis of HIV/AIDS.

The medicines included in the report were selected based on recommendations from available WHO treatment guidelines. The list is not intended to be exhaustive but to broadly cover the most commonly used medicines or medicine categories, in order to ensure that combined with their own resources, purchasing agencies can have at their disposal all medicines and diagnostics required for the comprehensive treatment of HIV/AIDS.

Additional medicines are often provided as they may be helpful due to:

- Greater cost offset by greater safety, e.g. fluconazole instead of ketoconazole;
- Fewer unwanted adverse effects, e.g. alternatives to amitriptyline.

Paediatric formulations have been included wherever possible.

Antiretroviral therapy

Since October 2000, this report has included information on the availability and price range of antiretroviral medicines for use in Highly Active Antiretroviral Therapy. In resource - poor settings, it is critical that these medicines are used in conjunction with WHO treatment guidelines which are intended to support and facilitate the proper management and scale-up of ART in the years to come, by proposing a public health approach to achieve these goals.

The topics addressed in the treatment guidelines include when to start ART, which antiretroviral regimens to start, reasons for changing ART, and what regimens to continue if treatment needs to be changed. They also address how treatment should be monitored, with specific reference to the side effects of ART, and make specific recommendations for certain patient subgroups.

The newly recommended first -line ARV regimens in adults and adolescents consist of a thymidine analog nucleoside reverse transcriptase inhibitor (NRTI) [stavudine (d4T) or zidovudine (ZDV)], a thiacytidine NRTI [lamivudine (3TC)] and a non-nucleoside reverse transcriptase inhibitor (NNRTI) [nevirapine (NVP) or efavirenz (EFV)].

The full text of the treatment guidelines can be found at: http://www.who.int/3by5/publications/documents/arv_guidelines/en/

Antituberculosis medicines

This report does not include data on sources and prices of medicines for first line treatment of tuberculosis (TB) as this information is available on the website of the International Price Indicator Guide 2003¹¹ or of the Global Drug Facility at http://www.stoptb.org/GDF/drugsupply/drugs.available.html.

¹¹ The International Price Indicator Guide 2003 is a joint publication of MSH and WHO. For more information refer to Annex 4, Websites: Drug Prices.

Further resources for information on TB can be found in Annex 3, including links to the DOTS-plus for multidrug resistant TB website and the prequalification of TB medicines.

1.7 Offers of medicine donations and price reductions

Public pressure, advocacy, competition from generic manufacturers and initiatives from pharmaceutical companies have led to reduced prices of some medicines for developing countries. There is no systematic approach to this equitable pricing. Each company determines its own eligibility criteria for countries, sectors and institutions that may benefit from its reduced price. Some companies offer donations of medicines for specific indications such as to prevent mother-to-child transmission of HIV, or to treat certain opportunistic infections affecting PLWAs.

The prices that are quoted in Chapter 4 of this report do not necessarily reflect all agreements that may have been negotiated with individual countries. Information on price offers for ARVs publicly announced by pharmaceutical manufacturers, including information on countries eligible for the offers and other conditions, can be found in the MSF report Untangling the web of price reductions: a pricing guide for the purchase of ARVs for developing countries (see Annex 4). Apart from providing prices of ARVs as offered by originator companies and selected generic companies, it highlights the lack of standardization among different companies on eligibility and terms and conditions of price offers. For example, some companies use UNCTAD classification (Least Developed Countries), or the World Bank classification (Low Income/Middle Income Countries) or a combination of UNDP classification (Human Development Index) and UNAIDS prevalence data.

Figure 2. Some examples of taxes and mark-ups as a percentage of the import price.

Source: http://www.haiweb.org/medicineprices

1.8 Additional Methods of Cost reduction

In addition to generic competition and advocacy for the reduced pricing in line with the purchasing power of countries, important parallel avenues to be pursued by governments include the active use of compulsory licensing, government use of patents, and parallel importation¹².

¹² For further details, refer to the practical guide “HIV/AIDS Medicines and related supplies: Contemporary context and procurement” Chapter 2: Intellectual Property Rights: a Concise Guide. The World Bank, Washington, February 2004.

As agreed by the Member States of the WTO in 2001, Least developed countries (LDCs) are not obliged to enforce pharmaceutical patents until at least 2016¹³. LDCs should make use or avail themselves of this provision to purchase lowest cost medicines on the world market. For valuable and concise information on this subject, please see the MSF report Drug patents under the spotlight: Sharing practical knowledge about pharmaceutical patentsand HIV/AIDS medicines and related supplies: Contemporary context and procurement.¹² Alternatively, to obtain further guidance from the appropriate organisation, please fill in the feedback form in Annex 5.

¹³ Doha Declaration on the TRIPS agreement and Public Health, paragraphs 6 & 7

The Global Fund to Fight AIDS, Malaria and Tuberculosis “encourages recipients to comply with national laws and applicable international obligations in the field of intellectual property including the flexibilities provided in the TRIPS agreement and referred to in the Doha Declaration in a manner that achieves the lowest possible price for products of assured quality.”¹⁴

¹⁴ The Global Fund to Fight AIDS, Tuberculosis and Malaria, Report of the Third Board Meeting, GF/B4/2, page 25, para 10 (a).

Other measures may include reducing or eliminating import duties and taxes. As data clearly demonstrate, these factors can severely distort the prices patients will pay for medicines compared with the price at which they were sold (see Figure 2). Increasing demand through pooled procurement may also be an option for purchasers to explore.

1.9 Other price information projects

1.9.1 Medicine Prices: a new approach to measurement

Initiated at the WHO-NGO Round Table in 2000, this project has developed technical guidance for a standard approach to the measurement of the prices people pay for key medicines. Availability and retail prices are recorded for a core list of 30 widely used medicines in their originator brand, most-sold and lowest-priced generic versions. Supplementary lists with different medicines can be tailored to meet local needs using the same method.

Price information is collected at a sample set of pharmacies in public, private and one other sector which can be defined to fit local conditions (eg. NGO agencies, religious missions or other charity services, or other types of not-for profit service providers). The method uses median prices provided by Management Sciences for Health (MSH) for the core medicines as a benchmark and the spreadsheet (CD-ROM included) calculates price ratios for each medicine to the MSH “reference” price.

The principal add-ons or “price components” between the manufacturer sales price and retail price are estimated for selected medicines, and treatment affordability is calculated for ten common conditions, relative to the daily wage of the lowest paid government worker. The concept of affordability is especially important, because it allows to evaluate “access” by referring to the actual income of the individual, according to a patient-focused approach.

A manual and accompanying spreadsheet on CD-ROM are freely available in English, French and Spanish on the web sites of both WHO: http://www.who.int/medicines/library/prices.shtml and Health Action International: http://www.haiweb.org/medicineprices/Arabic and Russian versions will be produced in the course of 2004.

The HAI website also contains an open-access repository of data from studies undertaken so far, and a synthesis of results from the nine pilot studies.

1.9.2 Price monitoring of pharmaceutical starting materials

With today’s immense flow of information, finding the right source for unbiased, accurate and timely market intelligence can be difficult, costly and time-consuming. Identifying the right source of information is the first step toward maximizing international business opportunities. The Market News Service (MNS) of the UNCTAD/Interna-tional Trade Centre (ITC) strives to fill this need by providing detailed price and market information on selected primary and semi-processed products of particular interest to developing countries and economies in transition, including a monthly report on Pharmaceutical Starting Materials of Essential Drugs.

The Market News Service (MNS) for Pharmaceutical Starting Materials was established in 1992 in collaboration with the Essential Drugs and Medicine Policy (EDM) of the World Health Organization (WHO) to issue a monthly report providing up-to-date prices and supporting commercial data on pharmaceutical starting materials used in the production of essential medicines. The report of December 2003 listed 303 active pharmaceutical ingredients. The report is an information source with the sole aim of improving market transparency and encouraging price and quality competition for the benefit of all market players. It covers the main trading centres in Europe and Asia and draws information from a network of price information providers.

The prices of active pharmaceutical ingredients used in manufacturing antiretrovirals have been significantly reduced during the last two years as shown in the graph below.

Figure 3. Price trends of various active pharmaceutical ingredients used in manufacturing antiretroviral medicines.

As part of its effort to provide information to improve market transparency, MNS reports are now directly available on-line through ITC’s latest market analysis tool, Product Map, www.p-maps.org, a subscription based service. Subscribers from least developed countries and WHO Regional Offices receive printed copies free-of-charge. The Product Map on Pharmaceuticals combines quantitative market information in relation to international trade statistics and macroeconomic indicators, qualitative market intelligence - such as market briefs and published market studies - and networking links to key market players in the pharmaceuticals industry.