Piramal Pharma Solutions recently announced that the Indian company has bolstered its highly potent API (HPAPI) capacity at its Riverview, MI manufacturing facility.

Investing about $10 million, the contract development and manufacturing organization (CDMO) has added two kilo labs as well as quality control and analysis labs. The factory, which makes HPAPIs with low occupational exposure levels (OELs) is now capable of producing highly potent compounds with OELs down to 1mcg/m3. The state-of-the-art site is designed with the required engineering controls and containment solutions to handle HPAPIs with OELs 1mcg/m³ and as low as 20ng/m³ at scales ranging from grams to 250 kilos. The new wing can manufacture materials at kilo lab scales with lots of 5 kilos.

The enhanced capability opens the site up to a new base of customers, including the antibody drug conjugate (ADC) market, according to Vince Ammoscato, vice president and Riverview site head.

ADCs comprise an antibody conjugated to a cytotoxic drug. The cancer-killing compounds are attached to the antibodies with linker technology. These innovative class of drugs combines the specificity of monoclonal antibodies for antigen-expressing tumor cells with small molecule anti-cancer drugs. Once the antibody is bound to the tumor, the chemical linker degrades, releasing the drug into the tumor. Since ADCs enable efficient delivery of cytotoxic drugs directly to targeted cells, they avoid potential damage to the normal cells—one of the major drawbacks associated with conventional chemotherapy.

Nearly half a dozen ADCs have already been approved by the FDA for commercial use and over 50 such products are currently undergoing clinical trials for various indications, such as refractory Hodgkin lymphoma, glioblastoma, small cell lung cancer, breast cancer, and ovarian cancer.

The cytotoxic “payloads” in ADCs are, usually, HPAPIs. Piramal offers a fully integrated solution for the ADC market—from proof-of-concept studies to conjugation development, clinical and commercial ADC GMP batch manufacturing and fill/finish.

The Riverview facility is equipped to develop HPAPI payloads and linkers. Then they are sent to the company’s Scotland site for the antibody conjugation, then back to Lexington, KY for sterile fill and finish, according to Ammoscato. This lends a strategic advantage for the CDMO. The company is planning more expansions in the coming days.

The need for creating additional manufacturing capacities for HPAPIs is driven by increasing demands for these compounds.

The global HPAPI market is expected to expand at a compound annual growth rate (CAGR) of 8.7% to $26.84 billion in 2023 from $17.72 billion in 2018, forecasts a report by Markets and Markets. The rate of growth of HPAPIs can be even higher to the tune of 10.3% per annum touching $34.8 billion by the year 2025, estimates Grand View Research.

Projections of the market value of HPAPIs vary. But the share of highly potent drugs in development is obviously on the rise. Treatments against cancer lead the global pharmaceuticals pipeline. And the oncology segment is where the largest proportion of HPAPIs are used in, reports indicate.

There are not many players around who have mastered the art and science of making HPAPIs. It is fewer so when it comes to the contract manufacturing space. This is because the production of HPAPIs involves complex processes and containment facilities requiring highly skilled manpower. Extensive capital investments are needed for the development of such a cGMP facility.

Captive manufacturing occupies the lion’s share in the HPAPI market as innovative companies prefer to maintain them in-house.

The trend is changing now. While resource constraints to build high containment facilities compel small and medium companies to look for contract service providers, larger firms prefer outsourcing in earlier development stages.

Also, reports say that some of the firms with HPAPI capacity are divesting their facilities in favor of outsourcing to CDMOs with integrated capabilities.

All types of companies see the value of developing strategic relationships with integrated CDMOs, according to Stuart Needleman, chief commercial officer, PPS. Sponsor companies are challenged by limited budgets and have to work smarter to remain competitive and outsourcing integrated services is a way to advance multiple candidates faster.

Pfizer, Novartis, Sanofi, Roche, Bristol-Myers Squibb, Boehringer Ingelheim, Teva, Eli Lilly, Merck, AbbVie, Mylan and Bayer are among the leading producers.

The emerging markets of India and China are expected to boost the demand for HPAPIs in the forecast period, according to Grand View.

Anticipating greater demand, Piramal is planning to make the Riverview facility operational round the clock, 24 hours a day, instead of the current twelve hours a day, seven days a week. The company bought the Ash Stevens operations in 2016 for $53 million plus milestone payments.