Understanding the requirements for High-Potency API (HPAPI) manufacturing and related cost efficiency is critical for pharmaceutical manufacturers and contract manufacturing organizations (CMOs) interested in expanding or adding high-potency active pharmaceutical ingredients capacity.
The most important issue in the high-potency sector especially for smaller companies is the capital expenditure. This is because the production of high-potency APIs is an expensive business and one has to decide whether to invest in barrier isolation technology or to use the more traditional personal protective equipment procedures. How they deploy their capital is a crucial issue for success of smaller companies.
Considering the strong potential and growth in the oncology drug market, contract manufacturers of APIs and formulation services are investing heavily in high-potency manufacturing.
Companies like SAFC, an industry leader in high-potent API manufacturing, Asymchem Laboratories and Cambrex are giving due weightage to understanding the requirements for HPAPI manufacturing and related costs while undertaking expansions.
Asymchem Laboratories, a contract manufacturer of API's and intermediates and drugs has opened its high potency active pharmaceutical ingredient (API) facility in TEDA Tianjin, China.
The dedicated facility at TEDA Tianjin location provides the state-of-the art containment for the production of potent APIs, as well as tablet and capsule manufacturing. The new facility allows Asymchem to operate two separate API manufacturing trains of 50L and 100L, as well as additional facilities for smaller-scale research and production and oral dosage form manufacturing.
Cambrex is also banking on growth in contract manufacturing of small-molecule active pharmaceutical ingredients (APIs) but with a decidedly valued-added offering. Although contract manufacturing of APIs and intermediates has long been a mainstay of the company, Cambrex is emphasizing value-added services such as drug-delivery technologies and a focus on contract manufacturing of specialized APIs such as high-potency compounds and controlled substances as part of its growth strategy.
As far as SAFC is concerned, the company has invested $75 million recently to expand its HPAPI capacity. These investments include a $4.5-million project to add a CGMP pilot plant and kilo-laboratory capacity at its Madison, Wisconsin facility, a $29-million investment to expand bacterial and fungal fermentation-derived HPAPI capacity at its site in Jerusalem and a $30-million investment to build a new commercial-scale HPAPI facility at Madison. SAFC also commissioned a conjugation suite for HPAPIs in September 2008. It invested $12 million for expanding its viral manufacturing capacity at its facility in Carlsbad, California. This expansion is to become operational in the second half of 2009.SAFC is also building a new commercial-scale HPAPI plant in Madison following several expansions at its facility there.
Even as the US and European pharmaceutical industry sees little growth prospects in API manufacturing, Asian producers are seeing high growth rates, both from domestic demand and export sales. According to an estimate Chinese API producers are projected to make sales of $9.9 billion in 2010 and Indian API producers are projected to grow to $4.8 billion in 2010.
While Chinese pharmaceutical companies are primarily oriented towards supplying their own domestic market, Indian API manufacturers are focused on export sales to highly regulated global markets.
To Asian API producers, particularly those that are exporting to global regulated markets manufacturing efficiency is becoming increasingly important. It means improving equipment utilization, improving yield, reducing process time, reducing harmful emissions and increasing reuse and recycling.
The Indian API manufacturers were early adapters of some new approaches such as using enzymatic catalyst platforms as an alternative to complex synthesis. The innovative efforts are often driven by the fact that Indian companies frequently compete as generic producers in markets with a high degree of price competition.
Here it must be mentioned that continuous processing offers the potential for reduced consumption of raw materials as well as smaller work-in-process inventories. It should also require less capital investment and take up less floor space. Micro reactors utilize small geometries to maximize the benefits of mass and particularly thermal transfer in fast reaction processes. Currently, the implementation of these innovative approaches in manufacturing plant remains low in a traditionally conservative industry, where the stirred tank reactor has reigned supreme for so long.
As awareness and understanding of where best to use and how to integrate these approaches increases, acceptance of such new methods can be expected to increase over the next five to 10 years. These approaches have the potential to completely revolutionize the production of small molecule APIs.
Asian pharmaceutical companies are now the world's lowest-cost producers of small-molecule APIs. With the tremendous pressure to reduce global healthcare costs, there is no doubt that Asian API manufacturers will play an increasingly prominent role in the global pharmaceutical market.
Improving facility design, equipment, engineering controls and the proper operation of facilities and equipment are essential to achieve the desired level of containment in HPAPI manufacturing.
Operator safety is also critical and involves the use of personal protection equipment, related training in handling HPAPIs, and implementation of safe-handling practices and current good manufacturing practices (cGMPs) to prevent operator exposure and contamination.