International Strategies for Tropical Disease Treatments - Experiences with Praziquantel - EDM Research Series No. 026
(1998; 113 pages) View the PDF document
Table of Contents
View the documentAbstract
View the documentAcknowledgments
View the documentInformation on authors
View the documentExchange rates used in the report
Open this folder and view contentsChapter 1: Policies for praziquantel*
Open this folder and view contentsChapter 2: Bayer & E. Merck: Discovery and development of praziquantel*
Open this folder and view contentsChapter 3: Shin Poong Pharmaceutical Co.: Process development in the Republic of Korea*
Open this folder and view contentsChapter 4: The Egyptian International Pharmaceutical Industries Co.: Praziquantel formulation*
Close this folderChapter 5: The international supply of praziquantel*
View the documentProducers and formulators
View the documentGlobal distribution of praziquantel
View the documentReferences
Open this folder and view contentsChapter 6: Demand for praziquantel and national distribution*
Open this folder and view contentsChapter 7: Prices and production costs of praziquantel*
View the documentOther documents in the DAP Research Series
View the documentDAP Research Series No. 26
 

Producers and formulators

The major producers

Praziquantel has been available since 1978 in the European market (King and Mahmoud, 1989) - (although information is scanty on when it was introduced in different European countries) - and has been registered and licensed for use in the USA since 1982 (Scrip, 1981). Until 1983, only two companies were marketing the product: Bayer, Germany (and its subsidiaries in France, the Netherlands, South Africa and the USA; and licentiates in Egypt, Indonesia, the Republic of Korea and Thailand), and E. Merck, Germany (and its subsidiary in South Africa; and licentiates in South America). In 1983, the Korean company, Shin Poong, entered the praziquantel market-initially within the Republic of Korea and later in the global market, as described in Chapter 3.

Shin Poong developed its own production process for praziquantel-which differed from the original Bayer process in a critical step (see Chapter 3). Shin Poong was able to patent this process in a number of developing and developed countries worldwide, including in the Republic of Korea (Kim et al., January, 1983) and in the USA (Kim et al., February, 1985) (see Chapter 3 for dates of registration in various countries).

By the mid-1980s, the brand-name products of praziquantel (for human use) on the market were:

• Biltricide (600 mg) [Bayer];
• Cysticide (500 mg), Cesol (150 mg), Cestox (150 mg), Cenaride, Cisiticid [E. Merck];
• Distocide (600 mg), Cestocide (150 mg) [Shin Poong].

These three firms-Bayer, E. Merck, and Shin Poong-are considered the “major producers” of praziquantel in this report. According to our estimates, these firms represent the major share of global production of praziquantel (82% in 1993), as discussed below.

Formulators and other producers

From the late 1980s on, praziquantel was being formulated under license from Shin Poong by two other companies (EIPICO in Egypt, which started production in 1987; and GMC in the Sudan, which started production in 1994) (see Chapters 3 and 4). On the expiry of the Bayer-E. Merck patent (which has been expiring in various countries since 1989, as noted in Chapter 2), the production process for praziquantel was included in the US Pharmacoepia (US Pharmacoepia, 1993-USP No. 22), and the product became available in generic form. A number of generic producers refer to the USP No. 22 production process for praziquantel as the basis for their own manufacturing of the active ingredient. Moreover, the raw materials required for the formulation of the tablets are now freely available in the international market from several sources, including from the major producers. Sources of raw materials for the formulation of praziquantel are listed in the International Trade Centre’s Market News Service (MNS), a publication that is co-managed by UNCTAD/GATT and WHO/DAP, currently funded by WHO/DAP.

A number of other producers and formulators of praziquantel emerged in the late 1980s and early 1990s. These firms include Medochemie in Cyprus, Pharmamed in Malta (a subsidiary of the International Dispensary Association - IDA), Dae-Woong in the Republic of Korea, Laboratoria Wolfs and Pharmachemic in Belgium, Athlone Labs in Ireland, and Chempharma and Rivopharma in Switzerland. Praziquantel is also currently being produced by a company in Shanghai, China, as Pyquiton (200 mg tablets), entirely for domestic use. We found no evidence of any export of the Chinese product, although the raw materials are exported (and reportedly are used by some formulators of praziquantel). In the 1980s, there were three Chinese manufacturers (Shanghai Pharma Factory # 6, Nanjing, and Tiangsang factories), but two of them stopped production, suggesting that the Chinese companies did not find the market profitable. Not much is publicly known about the production process used by the Chinese firm that continued production. EIPICO, however, reported that it tested and rejected the Chinese raw material for praziquantel on the basis of quality (see Chapter 4).

Our study found verbal reports that praziquantel has been produced or formulated by companies in other countries (including Italy, Japan, Russian Federation, Switzerland and Thailand), but details of the companies and their production processes were not available. These companies probably have limited production capacities. Many of the products, particularly those produced in developing countries, are reportedly of untested or dubious quality, and therefore, WHO has not approached these companies for procurement (Interview No. 8). Sales of these products (for example, sales of praziquantel produced by Thai companies) are probably directed mainly to domestic markets, and, to some extent, to markets in other developing countries.

We obtained verbal reports that some international agencies, bilateral agencies, and developing countries have procured drugs from generic producers in some developed countries in the past (an unnamed Italian company; and the two Swiss firms, Rivopharma and Chempharma). If current trends are an indication, generic production is likely to increase significantly in the future, particularly with the expiry of the Bayer patent (between 1989-1994 in most developed and several developing countries) and the Shin Poong process patent (in 1997 in the Republic of Korea, and by 2004 in most other countries). The major producers are already exploring mechanisms to introduce generic versions of the drug, as discussed below. This expansion of the generics market should auger well for the price of the product on the international market.

Production capacity and markets of major producers

As part of this study, all the known producers and formulators of praziquantel were contacted for information on the manufacture, marketing, and pricing of their products. An initial mailing of a questionnaire was followed up by telephone interviews in all cases, and by in-person interviews (when feasible) with firms that agreed to participate in the study. In general, firms were reluctant to provide information about their production processes, pricing structures, and sales figures. However, the three major producers, Bayer, E. Merck, and Shin Poong, along with EIPICO, all agreed to cooperate with the study, to provide internal data on production, pricing, and sales, and to meet with members of the study team. Other firms, mostly formulators, refused to provide data and often refused to cooperate.

Based on the data collected, we were able to calculate the first public estimate of the total global production of praziquantel, and the first estimate of total global supply of praziquantel tablets for use in the treatment of human schistosomiasis. We assumed that 1 kg. of raw material yields approximately 1600 (600 mg) tablets (allowing for an approximate 3% production loss from the normal 1:1 ratio of conversion of raw material to tablets). This assumption allowed us to estimate a total global production of 89 million tablets of praziquantel in 1993. Table 5.1 summarizes our calculations of the global production of praziquantel.

Table 5.1: Estimates of global praziquantel production (1993)


Volume of raw material (in tons = 1000 kgs)

No. of tablets (millions) [including tablets manufactured by subsidiaries, licentiates, and formulators]

% of global total

Major producers




E. Merck

1.5

2.4

2.7%

Bayer (using raw materials from E. Merck)

13.5

21.6

24.3%

Shin Poong

30.5

49a

55%

Other producers




China & othersb

10

16c

18%

World total

55.5

89

100%

a Includes tablets formulated by EIPICO (about 10 million tablets).
b Includes production of raw materials by Medochemie.
c Includes tablets formulated by Pharmamed, the IDA subsidiary.

Assumptions:

1. Estimates of total production of raw materials are based on data collected in interviews with company officials.

2. We estimate that the 3 major producers were responsible for 82% of total global production of raw materials in 1993 (45.5 tons of the total 55.5 tons of raw materials produced).

3. The number of tablets is based on a conversion factor of 1600 tablets from 1 kg of raw materials, which includes 3% production losses.


Figure 5.1: Global production of praziquantel (1981-1993: Based on Raw Material Production)

From 1981 to 1993, the global market for praziquantel underwent a dramatic transformation. Prior to 1983, the praziquantel market was provided solely by Bayer and E. Merck, with a total supply of approximately 8 million tablets of praziquantel a year. With the entry of Shin Poong in 1983, the market situation began to change rapidly. The global market share of Shin Poong increased consistently each year. In 1985, Bayer and E. Merck had about an 80% share of the market, producing about 10-15 tons of raw materials for praziquantel out of the estimated global total of 12.5-19 tons, with Shin Poong producing the balance. By 1990, Bayer and E. Merck’s share of the market had dropped to 60%, with their production of raw material totalling 15 tons of the estimated global total of 25 tons. In the early 1990s, Shin Poong overtook the original producers and became the dominant producer and global supplier of praziquantel.

The most recent production figures show Shin Poong’s striking dominance of the praziquantel market. In 1993 (see Table 5.1), Shin Poong was estimated to be producing about 30.5 tons of raw materials, out of a global total of 55.5 tons of raw materials (or in tablets: about 49 million of the total global production of 89 million praziquantel tablets). Figure 5.1 gives the estimated market shares of the major producers in 1993: Shin Poong (55%) and Bayer/E. Merck (27%). In addition, in 1993, the Chinese company was estimated to have a 13% share of the praziquantel market, while the other producers had an approximate 5% market share. The production data show that the entry of formulators and generic producers has significantly altered the global structure and composition of the praziquantel market, although these firms still represent a small proportion of the total global supply. These statistics also express the recent stagnation of Bayer and E. Merck, and the stunning growth of Shin Poong in the global market for praziquantel. The current production volumes, sales, and markets of the three major producers are described below, followed by a brief discussion of formulators and generic producers.

Bayer

Praziquantel sales constitute an insignificant share, possibly 0.001%, of the overall pharmaceutical sales of Bayer worldwide, estimated at US$ 10.5 billion. Bayer has 88% of its total pharmaceutical sales within only 8 countries: 6 countries in Western Europe, plus Japan and the USA. About 12% of all sales are to the remainder of the world, and only 4% of Bayer’s pharmaceutical sales are to developing countries. Most of these sales go through private markets, although a small proportion is sold through tenders to governmental or institutional markets (Interview No. 2).

Praziquantel sales constitute a small 0.2% of all sales to the Third World. Between 80-85% of these developing country sales (in contrast to E. Merck’s sales of praziquantel, and unlike Bayer’s sales of other pharmaceuticals) are through competitive tenders, and directed towards institutional markets. Since the mid-1980s, competitive producers (such as Shin Poong) have offered lower priced praziquantel on the global market; from this point on, Bayer has had to compete on price, with considerable losses in market share.

Bayer currently provides raw materials (obtained from E. Merck) to a number of developing countries, including Egypt, Indonesia, the Republic of Korea and Thailand, for local production of Biltricide under license. Licentiates receive know-how as well as raw materials from Bayer. Local production of praziquantel is probably most important in terms of volume in Egypt (where Alexco formulates praziquantel under license from Bayer, with volume varying between 1.5 and 2 million tablets a year). Another country where praziquantel could be produced in the future by Bayer is India. In general, however, Bayer sees limited markets where this product could be manufactured in sufficient quantities to reap benefits of economies of scale.

E. Merck

In a 1978 contract between Bayer and E. Merck, it was decided that E. Merck would be responsible for producing the basic raw materials required in the formulation of praziquantel tablets. Further, the companies determined that they would each formulate and market praziquantel in their respective “historical” marketing areas in the developing world: E. Merck in Latin America, and Bayer in Africa and South East Asia (Interview No. 3). Thus, E. Merck sales have concentrated in the Latin American and European regions (praziquantel sales in these two regions constitute about 10% of the total global praziquantel sales of Bayer and E. Merck). Besides Germany, E. Merck has supplied praziquantel to Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela.

Nonetheless, praziquantel remains a minor product in the overall production of E. Merck. Moreover, the firm’s share of the global praziquantel market has been shrinking in the past decade. E. Merck’s limited role in the international trade of praziquantel could be due to the way it produces and markets the drug. The raw materials are produced only in Germany; tablets are manufactured in Germany and, to some extent, in Latin America. Sales of praziquantel in Latin America, however, are relatively limited, because oxamniquine is the preferred drug for the treatment for schistosomiasis in those Latin American countries (especially Brazil) with significant prevalence of this disease (World Bank, 1989).

E. Merck’s current production capacity is between 25 and 28 tons. The actual production of the basic compounds is just over half of that amount, or about 15 tons, at a production cost of US$ 170 per kilogram (Interview No. 3). According to its agreement with Bayer, E. Merck retains about 10% of the raw materials for the formulation of praziquantel tablets to be sold in Europe and Latin America. The other 90% is passed on to Bayer for the formulation of praziquantel tablets that are sold to countries in Africa, Asia, Europe and North America.

According to interviews at E. Merck, the lowest price that the firm can set for praziquantel raw materials (US$ 170 per kg) is 50 per cent higher than the prices at which the raw materials are offered by other world market suppliers, because of E. Merck’s higher production costs (Interview No. 3). E. Merck has no current plans to expand its production capacity or its production, because the firm produces primarily for the private market, which is not growing. Less than 20 percent of E. Merck’s production is sold on tender bids. E. Merck has a competitive disadvantage in the tender market, since purchase decisions are made based primarily on price.

According to company representatives, two future scenarios are possible: the company could market aggressively and expand sales to its current capacity; or the company could work more closely with international agencies, expanding capacity beyond its current size, so that it could reengineer for larger quantities, produce at a lower cost, and compete effectively. According to E. Merck’s representatives, option one, of marketing enough praziquantel to fully use the current capacity, would be a major undertaking, since E. Merck’s cost and pricing structure is much higher than that of its international competitors (see also Chapter 7). And option two, of creating additional capacity and expanding the production programme for praziquantel, would take about 10 years and would only be feasible with sales guarantees from international agencies.

Given this situation, does E. Merck plan to continue to produce praziquantel in the future? According to company sources, the answer is yes, in order to have a full line of products, and because praziquantel is a life-saving drug. The company is also making attempts to develop a lower cost production process. In addition, E. Merck has been working for the last five years with WHO and others to develop a new therapy that would combine another drug, albendazole, with praziquantel.

Shin Poong

Since its entry into the praziquantel market, Shin Poong has gone from strength to strength. The company successfully developed a new low-cost production process for praziquantel, with Korean government support (see Chapter 3).

Between 1991 and 1993, the production value of Distocide tablets (Shin Poong’s praziquantel brand used in schistosomiasis treatment) went up from 2305 million wons (approx. US$ 3.03 million) to 3943 million wons (US$ 4.88 million); the export value for Distocide tablets in the same period increased from US$ 1.2 million to US$ 3.6 million (see Chapter 3).

Shin Poong has continued to gain new overseas markets for its praziquantel products (Distocide and Cestocide, a praziquantel formulation used in treatment of flukes). Besides supplying international agencies (UNICEF and WHO) and other organizations such as IDA, Shin Poong has been supplying praziquantel, in raw material and tablet forms, to a number of developing countries, with China ranked as the top importer. In 1992, Shin Poong manufactured praziquantel raw materials in excess of 20 tons (see Chapter 3), making it the world’s largest producer. In 1993, Shin Poong was producing about 55% of the total praziquantel manufactured globally. In addition, as noted above, Shin Poong has licensed EIPICO (Egypt) and GMC (Sudan) to produce the drug in their countries and for export (see Chapter 3).

Formulators and generic producers

Among formulators and generic producers of praziquantel, EIPICO’s entry into the market in 1987 was the most significant development, because of the size and importance of the Egyptian market for this product. Of the estimated total annual world market of 89 million tablets in 1993, Egyptian consumption of about 10 million tablets comprises over 11%. From 1990 on, EIPICO won the Egyptian government’s contract for the procurement of praziquantel (which constitutes more than 75% of total sales in Egypt), giving EIPICO a hugely dominant position over Alexco, Bayer’s licensee in Egypt. In 1992, EIPICO sales totalled almost 8 million tablets of praziquantel-about 7 million in the public sector and 1 million in the private sector (Chapter 4). Alexco’s total sales of praziquantel in Egypt (all in the private market) are estimated at about 1.5 to 2.0 million tablets.

Limited data were obtained for two other generic producers: Laboratoria Wolfs in Belgium, and Medochemie Pharmaceuticals in Cyprus. Laboratoria Wolfs started production of praziquantel in 1991, and only manufactures praziquantel for human use. The company produces its own raw materials based on USP 22 specifications, and also formulates the drug from raw materials supplied by its customers. Praziquantel constitutes approximately 2% of its overall sales of drugs.

Medochemie Pharmaceuticals, according to its representatives, has been producing praziquantel for the last 10 years, averaging 4-5 million 600 mg. tablets per year. Medochemie produces its own raw materials for praziquantel using its own technology. The company reportedly has the capacity to increase production to as much as 25 tons of praziquantel raw materials or approximately 40 million tablets annually. The company does not consider praziquantel sales as important, compared to overall drugs and pharmaceutical sales. Medochemie considers Bayer and Shin Poong as its main competitors in the praziquantel market. The company is currently supplying praziquantel to WHO, and could supply UNICEF in the future. It also supplies the drug to relief agencies that provide praziquantel to developing countries. Medochemie has also supplied several developing countries directly, but declined to identify these countries.

Unfortunately, we could obtain only limited data from the International Dispensary Association (IDA), which formulates praziquantel in its subsidiary (Pharmamed) based in Malta, and is a significant player in the global supply of praziquantel. IDA is a “foundation for non-profit procurement of medical supplies,” according to an IDA brochure (IDA, n.d.). The organization’s managing director, however, did not provide us with any data on its procurement sources or its production volumes of praziquantel, stating that those figures by product “are regarded as being confidential and can not be shared” (den Besten, March 1996). Our estimates of IDA’s role in the praziquantel market, therefore, are based on other sources.

to previous section
to next section
 
 
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human Info NGO. Last updated: November 5, 2014