CDMO/CMO Report: High-Potency Manufacturing
High-potency manufacturing, for both active pharmaceutical ingredients and drug products, continues to be an active area of investment by CDMOs/CMOs. What are some key moves, both recent and announced expansions by CDMOs/CMOs?
Roundup of recent investments in high-potency manufacturing
A roundup of recent investments by CDMOs/CMOs in high-potency manufacturing (high-potency active pharmaceutical ingredients [HPAPIs] and drug products) is outlined below.
WuXi STA. In July (July 2022), WuXi STA, a CDMO of APIs and drug products and 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 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.
In September (September 2022), WuXi STA opened a high-potency oral drug product manufacturing facility at its site in Wuxi, China. The facility offers multiple formulation processes, including wet and dry granulation, tablet compression and coating, and capsule filling, with an annual production capacity of 400 million tablets and 200 million capsules. Separately, WuXi STA is slated to open a new high-potency sterile parenteral production plant in the third quarter of 2023 at its Wuxi campus.
MilliporeSigma. In July (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. In addition, the company announced last 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 July (July 2022), Piramal Pharma Solutions, a CDMO of APIs and drug products, opened a new API manufacturing plant at its site in Aurora, Ontario, Canada, which includes HPAPI capabilities. 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 advanced a $32-million expansion at its site in Riverview, Michigan, for API development and manufacturing. The expansion consists 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 potent compounds. The expansion was slated for operation 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. In September (September 2022), Lonza announced that it had completed the expansion of its HPAPI multipurpose manufacturing suite at its site in Visp, Switzerland. The new HPAPI suite enables handling compounds with occupational exposure levels down to 1 ng/m3. Equipment onsite includes reactor sizes from 1 L to 50 L with a temperature range of -80 °C to +150 °C, isolation and drying equipment, and lyophilization and chromatography equipment for the manufacture of payload-linkers.
As part of a CHF-20 million ($22-million) expansion of its API manufacturing center in Nansha, China, Lonza added laboratories to develop and manufacture HPAPIs. The expanded laboratories and manufacturing facilities at Nansha were slated to come on line between the first and third quarters of 2022.
Polpharma API. Polpharma API, a Starogard Gdanski, Poland-based CDMO, is investing in a new R&D & production facility for HPAPIs. Completion of this investment is scheduled for the first quarter of 2024. It will include separate process laboratories, analytical laboratories for quality-control analyses, and a GMP kilo-lab production line with volume up to 1.5 kg with potential for volume increases.
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.
Nanoform. Nanoform, a provider of nanoparticle technologies, formulation development, and manufacturing services, recently invested in a GMP manufacturing facility expansion at its site in Helsinki, Finland, by adding two additional manufacturing suites, together with GMP analytical characterization laboratories, which can handle highly potent compounds to less than 30 ng/m3.
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-PharmaZell. Novasep-PharmaZell is investing a total of EUR 51 million ($55 million) at four of Novasep’s 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. Novasep-PharmaZell was formed in April (April 2022) following the merger of the two companies, Novasep and PharmaZell, both CDMOs of APIs.
In July (July 2022), Novasep-PharmaZell Group begun a EUR 7.3-million ($7.4-million) investment to expand its Mourenx, France, site to create a multi-purpose pilot workshop within one of its production units. The investment includes an upgrade of two existing 2,000-liter reactors and the addition of a new 1,500-liter reactor and Hastelloy filter-dryer. The new multi-purpose workshop will be equipped to produce batches ranging from 30 kg to 100 kg for clinical trials, process validation, and commercial production of active pharmaceutical ingredients (APIs) for targeted therapies, with a focus on HPAPIs.
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) for HPAPIs with an investment of approximately EUR 10 million ($11 million) at its site in Rodano (Milan), Italy. 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. Timeline for completion and start-up is 2023. In September (September 2022), the company began an expansion of its Mahad, India, manufacturing site, to install a new high-containment production line for containing and handling substances up to level OEB4 (up to 1µg/m3). The new line will be suitable for producing medium-volume batches.
PCI Pharma Services. In July (July 2022), PCI Pharma Services, a CDMO of drug products and a contract packager, announced a multi-million-dollar expansion of its site in Tredegar, Wales, UK, to add two new facilities for manufacturing and packaging of solid oral-dose tablets and capsules for high-potency products. The expansion will double large-scale processing capacity, including dispensing and fluid-bed granulation of high-potency solid-dose products at the commercial scale. In addition, there will be a new high-potency, multi-product packaging facility with primary and secondary blistering and bottling suites. The expansion is slated to be operational in the fall of 2022.
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, which allows for occupational exposure limits up to 30 ng/m3 and enables manufacture up to 35-kg batch size. The new plant features reactors up to 1,000 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 facility in Taiwan. 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 1,000 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. BSP Pharmaceuticals, a Latina Scalo, Italy-based CDMO of APIs and drug products, is progressing expansions for drug-substance and drug-product manufacturing for both cytotoxic and non-cytotoxic compounds, which includes two additional sterile suites for manufacturing cytotoxic compounds, and two new conjugation suites.
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. Last November (November 2021), CordenPharma, a CDMO of APIs ad drug products, announced an investment for a new GMP Clinical Trial Development facility for the manufacturing of oral solid dosage drug products at it facility in Plankstadt, Germany. CordenPharma Plankstadt is the company’s Center of Excellence for the Development & Manufacturing of Highly Potent Oral Solid Drug Products for compounds that have an occupational exposure limit of level < 1 µg/m3. The facility has a targeted completion date in the third quarter of 2022. Also, 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.
Note: currency conversions at the time of expansion announcement.
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