Contract Manufacturing of Highly Potent Compounds

Investment and production in HPAPI are expanding, but finding the right expertise is crucial.

by Susan Thompson, Technical Director at VxP Pharma

The high-potency pharmaceutical manufacturing industry continues to expand every year. The market for high-potency active pharmaceutical ingredients (HPAPIs), such as anti-cancer drugs, prostaglandins, opioids and hormones, is currently valued at 16.02 billion. Analysts expect the market to increase at a compound annual growth rate (CAGR) of 8.5 percent, to reach 24.09 billion by 2021.

Manufacturing high-potency compounds involves highly complex, expensive processes and facilities. These compounds also carry high risks of toxicity and contamination. These concerns have led many pharmaceutical companies to turn to contract manufacturing organizations (CMOs). In fact, more than 130 CMO facilities worldwide are now focused on HPAPI production, and their client lists are steadily growing.

Still, handling HPAPI formulations requires great attention to detail, intensive training, and a clear understanding of the risks at each step of the manufacturing process. This means pharmaceutical development firms need to take heightened care when choosing their CMO partners for HPAPI manufacturing, to ensure that they’re only partnering with organizations that bring the right level of expertise to the table.

A growing number of pharma developers are investing in HPAPI production.

The field of highly potent compound manufacturing has seen several positive market indicators.

Oncology drugs (one of the top categories of HPAPIs) were already the highest-valued therapeutic class of drugs in 2007, when they accounted for $41.4 billion, 6.2 percent of the total global pharmaceutical market. Sales of anti-cancer drugs like cytotoxic APIs have more than doubled since then, reaching $107 billion in 2015, with no end in sight for this sector’s explosive growth. Around 60 percent of all HPAPIs currently under development are focused on the treatment of cancer.

However, cancer therapies are only one driver of high-potency compound manufacturing. One of the most overarching trends in modern medicine is a gradual shift toward more targeted, potent treatments, which are biologically active even in small amounts. These treatments include therapeutic hormones, lipids such as prostaglandins, pain drugs such as opioids, and a wide range of other highly potent APIs for use in marketable compounds.

A growing number of pharma developers are investing in HPAPI production.

The ever-increasing demand for these specialized classes of drugs has driven seven- and eight-figure investments in HPAPI contract manufacturing, from major pharmaceutical development firms around the globe. Many of these CMOs manufacture not only the HPAPIs themselves, but also the antibody drug conjugates (ADCs) that link to the small HPAPI molecules, helping circulate them throughout the body and release them into targeted cells.

Over the past several years, pharmaceutical firms and CMOs alike have significantly increased their investments in HPAPI manufacturing. Large developers like ADC Biotechnology, Catalent, Novasep and Lonza have all spent millions on facilities for themselves and their subsidiaries. CMOs like Sigma-Aldritch and Feldker, meanwhile, have risen to the demand by investing heavily in expanding the current good manufacturing practices (CGMP) capacities of facilities around the world.

CMOs with expertise in HPAPI manufacturing are in high demand as partners.

Each HPAPI project entails its own unique set of steps and risks. In fact, quite a few HPAPI manufacturing processes involve new chemical entities (NCEs) that don’t come with detailed toxicity data. Some CMOs have in-house assessment systems and protocols for developing safety measures around NCEs, while many others have their own libraries of data on comparable substances. In any case, CMOs with significant experience assessing NCEs in terms of toxicity, carcinogenicity and other factors are at a premium in the current market.

Along with these types of expertise, CMOs with good track records of safe HPAPI handling have invested millions in specialized facility design. Single-pass air flow systems, including vestibules, airlocks, closed restricted air barrier systems (RABS), and pressure and filtration equipment, are all crucial. Good manufacturing practice (GMP) also dictates the use of personnel protective equipment (PPE).

Most importantly of all, every person in the pipeline needs to receive extensive training in synthetic organic chemistry, purification, analytical instrumentation, and safety protocols. HPAPI production carries significant risks of cross-contamination and exposure, which means awareness and common sense often prove to be some of the most valuable tools in any facility.

In the HPAPI sector, trust is an especially critical asset for any manufacturer. And as investment in high-potency development and manufacture continues to grow, many CMOs who’ve poured resources into bigger, better facilities and more extensive training are already reaping the benefits.