Richardson clarified the distinction between chemically produced drugs (e.g., cycloserine), which are relatively straightforward to scale up in terms of volume of production, and injectable drugs, which are fermentationbased and require freeze-drying of the active ingredient. Fermentation chemistry and freeze-drying are expensive and complex processes. Cassell remarked that such injectable MDR TB drugs are made by microorganisms and have associated problems with batches, reproducibility, and yields (and thus QA). Patrick Lukulay, Vice President, Global Health Impact Programs, U.S. Pharmacopeial Convention (USP), noted that manufacturing the API for SLDs is also very complicated and extremely expensive due to the crystallization steps required.
Need for systems strengthening and capacity building.30 SLDs for MDR TB are a particular challenge for pharmaceutical companies. Small volumes are required, they are expensive, and they are difficult to manage and to ensure proper treatment compliance. Sebbag stressed that reliable diagnosis and ensuring compliance are crucial for protecting SLDs from misuse, which can lead to further spread of MDR and XDR TB. In that vein, drugs are only one part of the MDR TB challenge, in that education and enhanced patient communication are also needed, calling for systems strengthening and capacity building, such as training programs, at all levels of the supply chain.
Using malaria treatment as an example, Sebbag described how a complex organizational structure of institutions, partners, and funding entities (which is similar to the MDR TB structure) makes facilitating communication among the multiple partners a challenge. One strategy for systems strengthening that is used in malaria treatment is capacity building to implement best practices at the local supply chain and case management levels to ensure that patients have access to QA drugs. Sebbag noted that this would require both workforce training and active partnership of all players in the SLD supply chain.
Perspective of a Midsize Pharmaceutical Company
Paul Ryu, Dong-A Pharmaceutical Co., Ltd., provided the perspective of a midsize pharmaceutical company. According to Ryu, Dong-A is currently producing drugs to meet 80 percent of the world’s demand for cycloserine; the company has made investments of about $3 million to upgrade its facilities and has already been inspected by WHO. He commented that the company is willing to make the investment to enter the
30 This subsection is based on the presentation by Robert Sebbag, Vice President, Access to Medicines, Sanofi.