CDMOs/CMOs Expand High-Potency API Manufacturing

Growth in the oncology drug market continues to spur demand for high-potency API manufacturing. Which CDMOs/CMOs are expanding? DCAT Value Chain Insights rounds up the latest investments.

Growth in the oncology drug market continues to spur demand for high-potency API manufacturing. Which CDMOs/CMOs are expanding? DCAT Value Chain Insights rounds up the latest investments.

Roundup of recent investments in HPAPI manufacturing
A roundup of recent investments by CDMOs/CMOs in high-potency active pharmaceutical ingredient (HPAPI) manufacturing is outlined below.

WuXi STA. Earlier this month (July 2022), WuXiT STA, a subsidiary of WuXi AppTec, opened a HPAPI plant at its site in Changzhou, Jiangsu Province, China.

The new plant consists of reactors from 250 L to 3,000 L, prep-HPLC systems, a 10-m2 tray lyophilizer, and flow-chemistry and milling technologies with capability to handle potent compounds with occupational exposure limits as low as 10 ng/m3.

WuXi STA has two sites located in Shanghai Jinshan, and Changzhou, China, to support the process development and manufacture of HPAPIs. In addition to HPAPIs, the Changzhou site provides process development and manufacturing for linkers, oligonucleotides, and peptides.

MilliporeSigma. Also, earlier this month (July 2022), MilliporeSigma, the life-science business of Merck KGaA, opened a new $65-million, 70,000-square-foot HPAPI manufacturing facility in Verona, Wisconsin. The new facility doubles the company’s HPAPI manufacturing capacity. The facility joins the company’s facility in St. Louis, Missouri, which specializes in antibody-drug conjugate (ADC) bio-conjugation, APIs, excipients, and adjuvants manufacturing. The company announced in November (November 2021) that it is expanding ADC capabilities at is clinical manufacturing facility in St. Louis, Missouri, to provide a larger footprint to enable large-scale production, including chromatographic purification for early-phase clinical supply. 

Piramal Pharma Solutions. In May (May 2022), Piramal Pharma Solutions, a CDMO of active pharmaceutical ingredients (APIs) and drug products, reported that a new API manufacturing plant at its site in Aurora, Ontario, Canada, came on line and successfully completed its initial production run. The new plant, built as part of a CAD $30-million (US$23-million) capital investment, has more than 10,000 square feet of new manufacturing space and includes two new reactor suites with additional filtration and drying capabilities. It also expands the company’s ability to produce clinical to commercial-scale APIs, including HPAPIs requiring an occupational exposure limit (OEL) of 1 mcg/m3.

In addition, Piramal is proceeding with a $32-million expansion, at its site in Riverview, Michigan, for API development and manufacturing. The expansion will consist of more than 25,000 square feet to include additional large-scale manufacturing, kilo labs, and process development capacity. Facility design procedures includes controlled-room pressurizations with air locks, glovebox technology/contained systems for charging and discharging of potent compounds. The expansion is slated to be ready in the summer of 2022.

The company is also expanding ADC capabilities at its facility in Grangemouth, Scotland. In the first phase of the Grangemouth site expansion, two new ADC manufacturing suites will be added and are slated to be operational by the third quarter of 2023. The building has been designed to accommodate further expansion, with planned future phases that include a new sterile fill–finish suite dedicated to ADCs and two additional large-scale manufacturing suites capable of handling increased batch sizes.

Cambrex. Earlier this year (April 2022), Cambrex completed a $50-million expansion of its large-scale API manufacturing capabilities at its facility in Charles City, Iowa. The start-up of the new manufacturing space is the culmination of a two-year project, originally announced in 2020, to increase the capacity of the facility by 30%. Following the expansion, the facility has approximately 400 employees and an installed reactor capacity of over 25,000 gallons. The facility is located on a 45-acre property and produces APIs and pharmaceutical intermediates, including highly potent molecules and controlled substances.

In addition to its expansion in Iowa, Cambrex is investing in additional small- and mid-scale API manufacturing capacity at its facilities in Karlskoga, Sweden, and High Point, North Carolina. New capacity at those facilities is expected to come on line in late 2022 and mid-2023, respectively.

A $30-million expansion in its High Point, North Carolina, facility will approximately double the facility’s capacity by adding new chemistry laboratories, new clinical manufacturing suites, and a small-scale commercial manufacturing operation with reactors up to 2,000 liters. In addition to expanding capabilities in continuous flow chemistry, the investment will give Cambrex the ability to develop and manufacture HPAPIs at the facility. The High Point facility expansion is slated to be completed during the first half of 2023.

HAS Healthcare Advanced Synthesis. HAS Healthcare Advanced Synthesis (formerly Helsinn Advanced Synthesis) has progressed a multi-year expansion for HPAPs. A investment of CHF 20 million ($22 million) in 2012 to 2014 was for a dedicated anticancer facility (Synthesis C) with three production bays ranging from 20 L to 800 L down to an occupational exposure limit of 50 ng/m³ in batch sizes ranging from 1 to 30 kg per batch. In 2019, this facility was expanded with a CHF 16.5-million ($17.9-million) investment to add a larger production bay with 800-L, 1000-L, and 1,200-L reactors, allowing for up to 40 kg per batch.  At the same time, the company’s R&D and quality control (QC) lab capacity was doubled. With an ongoing investment of CHF 8 million ($8.7 million) for a new QC Laboratory Center, building construction began this year (2022), and completion will occur next year (2023). This year (2022), the company initiated a CHF 70-million ($76-million) expansion (Synthesis D), which will have three different HPAPI bays to offer additional capacity.

AGC Fine Chemicals. AGC Fine Chemicals, a Tokyo, Japan-based manufacturer of glass, chemicals, and high-tech materials, is investing $100 million to expand AGC Pharma Chemicals Europe, an AGC subsidiary and synthetic pharmaceutical CDMO. A new building with a total floor area of 7,500 m2 will be constructed on the company’s site to increase current production capacity by 30%. The expansion will include the introduction of facilities for HPAPIs. The new facility is scheduled to start operation in the first half of 2024.

Lonza. As part of a CHF-20 million ($22-million) expansion of its API manufacturing center in Nansha, China, in laboratories and mid-scale manufacturing capacity, Lonza is adding laboratories to develop and manufacture HPAPIs. The expanded laboratories and manufacturing facilities at Nansha are coming on line between the first and third quarters of 2022.

Additionally, in December (December 2020), Lonza announced an investment to expand bioconjugation capacity at its site in Visp, Switzerland. The expansion will add two production suites in an existing bioconjugation facility for clinical and commercial supply. In addition, an extension to laboratory space will double analytical and process development capacity. The new capacity was slated to be fully operational from the first half of 2022. Also, in 2020/early 2021, Lonza opened two manufacturing suites for antibody drug conjugate (ADC)–drug-linker (payload) manufacturing at its site in Visp.

Carbogen Amcis. Carbogen Amcis, a Bubendorf, Switzerland-based CDMO of APIs and drug products, is proceeding with a CHF 15-million ($16-million) joint-funded agreement with an undisclosed Japan-based customer to expand its site in Bubendorf, Switzerland. Carbogen Amcis will produce exclusively for the signatory customer a complex HPAPI for a commercial ADC. The company expects to commence operations in the autumn of 2022.

Sterling Pharma Solutions. Sterling Pharma Solutions is investing £1 million ($1.3 million) to expand its bioconjugation and ADCs facility in Deeside, UK, to increase the current laboratory space from 275 to 419 square meters and reconfigure the layout to provide the ability to develop and expand areas in the future.

This investment supports the growth of the company’s ADC capabilities since it gained the 6,500 square-meter site in April 2021 as part of its acquisition of ADC Biotechnology and will add to its scientific and analytical teams and establishes cGMP bioconjugation/ADC manufacturing capabilities.  The work and expansion will allow for the recruitment of up to five additional scientists. The company is integrating the site’s quality management systems in line with its global practices and is now commissioning the quality control and manufacturing facilities in readiness for GMP certification, which the company anticipates will be in place by late 2022.

Ajinomoto Bio-Pharma Services. Ajinomoto Bio-Pharma Services is expanding its small-molecule manufacturing capabilities with the addition of a new production facility in Visakhapatnam, India. Construction of the 8,500-square-meter facility began at the end of July 2020 and was slated to be completed in mid-2022. The new small-molecule manufacturing facility doubles the production capacity at the site to 310 cubic meters for APIs and intermediates and has dedicated equipment to manage Occupational Exposure Band Level 4 high-potency ingredients.

Novasep. Novasep is investing a total of EUR 51 million ($55 million) at four of its European sites, located in France and in Germany, for API development and manufacturing. These investments, which will be completed in 2022 and 2023, include the modernization and addition of new API manufacturing workshops, the extension of clinical and commercial HPAPI capabilities, including ADC payloads and the addition of cGMP pilot-scale flow-chemistry capability. The company also earlier invested more than EUR 4 million ($4.8 million) to expand HPAPI manufacturing capacity at its site in Le Mans, France site.

Olon. Earlier this year (2022), Olon announced an investment of EUR 27 million ($30 million) in 2022/2023 to expand internal expertise and capacity for high-containment manufacturing.

The company recently completed a new large-scale high containment production line (OEL < 1 mg/m3) with an investment of approximately EUR 10 million ($11 million) at its site in Rodano, Italy. The new line enables Olon to produce HPAPIs in large-scale product batches ranging from 30 to 250 kg

Olon is investing EUR 13 million ($14 million) to add a new production line for HPAPI manufacturing and to expand a large-scale HPAPI production line at its site in Rodano (Milan), Italy. Timeline for completion and start-up is 2023. The investment will allow for a Safebridge 3B containment level corresponding to an occupational exposure limit (OEL) of OEL 0.03 μg/m3 for the new production line and an OEL of 1-0.1 μg/m3 for the expanded large-scale line.

In 2021, Olon completed a new large-scale HPAPI production line at its facility in Rodano, Italy (Milan). The line strengthens the synthesis, finishing and drying section to manage acid-based reactions and can produce batches up to 250 kg, with a containment band of OEB 5, for either highly active or highly toxic products (occupational exposure limit of 0.1-1 micrograms/m3)

Cerbios-Pharma. Cerbios Pharma, a Lugano, Switzerland-based CDMO, is expanding with a new manufacturing building dedicated to HPAPIs, which will host two additional cGMP production lines for cytotoxic molecules and additional space for dedicated R&D and quality control labs. The new cGMP unit (SafeBridge Category 4) will become operative in the second quarter of 2023 and will host production ranging from 200 mg to 2 kg per batch.

In 2021, Cerobis-Pharma received approval from Swissmedic, the national pharmaceutical regulatory agency in Switzerland, for the company’s new HPAPI production plant. The new production line is dedicated to highly active products with containment allowing occupational exposure limits up to 30 ng/m3 and enables manufacture up to 35-kg batch size. The new plant features reactors up to 1000 L and a pressure-filter-dryer.

Formosa Laboratories. Formosa Laboratories, a Taoyuan, Taiwan-based CDMO of APIs, ADCs and injectables, is investing $20 million to expand its API manufacturing facility to build up its bioconjugation ADC platform, a peptide-generation system for personalized medicine production, and a microfluidic synthesis system at its current facility in Taiwan. The expansion is expected to broaden the services spectrum for peptide development and microfluidic synthesis as well as advance capacity for HPAPIs and ADCs. The expansion began in January 2022 and is expected to be completed in 2023.

Sai Life Sciences. Sai Life Sciences is expanding to set up a dedicated facility for HPAPIs at the company’s manufacturing campus in India. This facility follows the company’s recent opening of a new HPAPI development facility at its R&D campus in Hyderabad, India. Being built with a project outlay of $3.6 million, the HPAPI manufacturing facility will have six reactors ranging from 100 L to 1000 L of various materials of construction (stainless steel/ Hastelloy/glass-lined). The 15,000-square-foot facility was slated to be ready in the second quarter of 2022.

BSP Pharmaceuticals. In June 2020, BSP Pharmaceuticals, a Latina Scalo, Italy-based CDMO, approved capital investments to expand its existing capacity for drug-substance and drug-product manufacturing for high-potent and cytotoxic compounds. On the drug-substance side, two conjugation suites were slated to operational at the end of 2021, and each one will add capacity for more than 420 kg monoclonal antibody (mAb) per annum. This expansion will more than triple current capacity for drug-substance manufacturing to 1,254 Kg mAb and will offer the possibility to scale up batch sizes.

Seqens. In 2020, Seqens inaugurated a HPAPI manufacturing unit at its site in Villeneuve-La-Garenne, France, with an investment of EUR 30 million ($35 million).

Corden Pharma. In October 2020, CordenPharma completed the addition of new HPAPI laboratory at its facility in Boulder, Colorado. The new laboratory is capable of handling highly potent compounds with an occupational exposure limit as low as 1 ng/m3.

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