The CDMO/CMO and Suppliers’ Report: Small-Molecule APIs
Which CDMOs/CDMO are expanding manufacturing capacity for intermediates and small-molecule active pharmaceutical ingredients (APIs)? DCAT Value Chain Insights gives a roundup of recently announced, in-progress, and completed expansions.
Expansions in peptides, oligonucleotides
A niche, but growing area of manufacturing expansions by CDMOs/CMOs is in peptides and oligonucleotides, with several companies announcing expansions in 2023.
Bachem, a Bubendorf, Switzerland-headquartered CDMO of peptides and oligonucleotides, is proceeding with a billion-dollar plus investment plan to increase manufacturing capacity across its sites, including new facilities. The company is constructing a new large-scale facility for the manufacture of peptides and oligonucleotides at its site in Bubendorf, Switzerland, with the commissioning of the new plant planned for 2024 with the first phase operational in 2024 and a second phase operational in 2026. By 2030, a further production site is planned at a new site in Sisslerfeld in the municipality of Eiken, Canton of Aargau, Switzerland. In all, Bachem is planning investments of CHF 550 million ($600 million) at its headquarters site in Bubendorf and CHF 750 million ($819 million) for the new site in Sisslerfeld/Eiken. Bachem is also investing in capacity expansions across its global manufacturing network at its sites in the following: Vionnaz, Switzerland; Torrance, California; Vista, California; and St. Helens, UK.
Last year (2023), Agilent Technologies, a Santa Clara, California-based technology company and CDMO of nucleic acid-based APIs, broke ground for a $725-million investment to double manufacturing capacity of therapeutic nucleic acids at its facility in Frederick, Colorado, by adding two new manufacturing lines. The new investment is in addition to a previously announced $150-million investment to add 25,000 square feet of manufacturing capacity to the Frederick facility. Agilent’s manufacturing facilities in Colorado produce siRNA, antisense molecules, and CRISPR-guided RNA molecules. The expansion is expected to be completed by the end of 2026.
Earlier this year (2024), WuXi STA, a CDMO of APIs and drug products, commissioned two new peptide manufacturing plants in China, one at its site in Changzhou and another at its new site in Taixing. The expansion has increased the company’s solid-phase peptide synthesis total reactor volume to 32,000 liters. With the announcement, the Changzhou site inaugurated its third peptide manufacturing plant. The other newly commissioned peptide plant is situated at the company’s Taixing site. Commissioning the peptide plant at the Taixing site marks its official launch as the company’s newest and largest of WuXi AppTec’s five API production sites.
Spanning a total area of 169 acres, the Taixing site is designed to manufacture a range of synthetic molecules, including small molecules, peptides, oligonucleotides, and conjugates. The Phase I construction includes nine plants with the total reactor volume exceeding 1,000 m3, including a dedicated plant for API cleanrooms. Once the Taixing site Phase I is fully operational in 2025, the company’s total reactor volume for small-molecule API and intermediate manufacturing will surpass 4,000 m3.
CordenPharma, a CDMO of drug substances and drug products, announced in 2023 that it is adding synthetic oligonucleotide manufacturing through a two-phase investment at its site in Colorado. Phase One involves reconditioning existing laboratory space, purchase of development equipment, and hiring a team to set up process and analytical development capabilities. Target completion was the fourth quarter of 2023. Phase Two, which was initiated at the same time as Phase One, includes the redesign of existing manufacturing space to create a fully GMP-compliant manufacturing area housing synthesis, cleavage, downstream processing, and lyophilization at the 10–100 mmol scale for early- to mid-phase clinical trial material supply. The introduction of oligonucleotide manufacturing at its Colorado facility is an extension of the company’s “Tides” capabilities, which includes peptide manufacturing. Last year (2023), the company inaugurated increased commercial peptide production capacity with newly upgraded facilities at CordenPharma Colorado, After kicking off capital investments in early 2023, CordenPharma successfully completed a series of upgrades and modernizations to the facilityto increase the efficiency and throughput of solid-phase peptide synthesis peptide production.
In addition, Euroapi, a spin-out company of Sanofi and a chemical API CDMO, acquired BianoGMP, a Gera, Germany-based CDMO of oligonucleotides, late last year (2023). Biano will retain its corporate brand and be a Euroapi company.
High-potency manufacturing expansions.
High-potency API (HPAPI) manufacturing continues to be an active area of investment by CDMOs/CMOS. Earlier this month (February 2024), Olon announced the construction of a GMP HPAPI suite at the company’s site in Concord, Ohio. The company’s Concord site is the company’s Center of Excellence for early development of APIs. The expansion adds to the company’s commercial-scale operations at its sites in Segrate and Rodano, Italy (near Milan).
Last year (2023), Olon started the construction of a new facility at its site in Rodano, dedicated to managing and producing ultra-potent compounds used as payloads and payload-linkers for antibody-drug conjugates (ADCs). Olon is investing EUR 22 million ($23.5 million) in the new facility. Upon construction of the new building, a second shell will be built containing the production facility and the quality control and research and development areas as well as all auxiliary facilities. The first phase of the construction, to build the payload research and development area is expected to be completed by the first half of 2024. Once completed, the company will move on to the second stage of finalizing the production line by creating the quality control and GMP production areas, with the installation of industrial production equipment. Also, in 2023, Olon completed an investment in its facility in Rodano to expand pilot-plant capacity for scaling up HPAPIs up to a level of containment of OEB5 (1-0.1 ug/m3).
Last month (January 2024), Piramal Pharma Solutions, a CDMO of APIs and drug products, opened its expanded ADC manufacturing facility in Grangemouth, Scotland, UK, with an investment of £45 million ($57 million). The expansion increased the site’s capacity by approximately 70% to 80% to enable scale-up of commercial ADC manufacturing batches. The capacity expansion features two new ADC manufacturing suites to complement the existing three and has been designed to accommodate further expansion. Potential future enhancements may include a new sterile fill–finish suite dedicated to ADCs and two additional large-scale manufacturing suites capable of handling increased batch sizes.
In 2022, Piramal opened a new API manufacturing plant at its site in Aurora, Ontario, Canada, which included 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. In addition, Piramal advanced a $32-million expansion at its site in Riverview, Michigan, for API development and manufacturing. The expansion consisted of more than 25,000 square feet to include additional large-scale manufacturing, kilo labs, and process development capacity.
WuXi STA opened in 2022 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 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 China, Shanghai Jinshan and Changzhou, 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, the life-science business of Merck KGaA, opened in 2022 a new $65-million, 70,000-square-foot HPAPI manufacturing facility in Verona, Wisconsin. The new facility doubled the company’s HPAPI manufacturing capacity. The facility joins the company’s facility in St. Louis, Missouri, which specializes in ADC bio-conjugation, APIs, excipients, and adjuvants manufacturing. In addition, the company announced in November 2021 an expansion of ADC capabilities at is clinical manufacturing facility in St. Louis to provide a larger footprint to enable large-scale production, including chromatographic purification for early-phase clinical supply.
In 2022, Lonza completed an expansion of its HPAPI multipurpose manufacturing suite at its site in Visp, Switzerland. In addition, 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.
Polpharma API, a Starogard Gdanski, Poland-based CDMO, is investing in a new R&D & production facility for HPAPIs. Completion is in 2024. It will include separate process laboratories, analytical laboratories for quality-control analyses, and a GMP kilo-lab production line with volumes up to 1.5 kg with potential for volume increases.
Carbogen Amcis recently invested CHF 15-million ($16-million) in a jointly funded project with an undisclosed Japan-based customer to expand its site in Bubendorf, Switzerland, to produce exclusively for the signatory customer a complex HPAPI for a commercial ADC.
Last year (2023), Sterling Pharma Solutions completed its acquisition of an API manufacturing facility in Ringaskiddy, Ireland, from Novartis. The 111-acre site includes multiple commercial-scale production buildings, with a total vessel capacity of 175 cubic meters across over 30 reactor trains, a small-scale facility, and a development and support building housing 14 development and analytical laboratories. The facility also includes capabilities for HPAPIs, solid-phase and agitated vessels for peptide coupling and synthesis, as well as various milling and micronization equipment for drug-substance processing.
Also, in 2023, the Medicines and Healthcare products Regulatory Agency (MHRA), the UK’s pharmaceutical regulatory authority, granted manufacturer’s authorization for investigational medicinal products to allow Sterling to manufacture ADCs for clinical use in its cGMP manufacturing facility in Deeside, UK. Sterling acquired the 6,500-square-meter site as part of its purchase of ADC Biotechnology in 2021, and has since gone on to invest in expanding the facility to develop its scientific and analytical teams, install a new water-for-injection plant, and establish bioconjugation and ADC manufacturing capabilities.
Axplora (formerly Novasep-PharmaZell) invested 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 were completed in 2022/2023, 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 2022 following the merger of the two companies, Novasep and PharmaZell, both CDMOs of APIs; the combined company was later renamed Axplora. Also in 2022, the company began 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.
In 2023, Sai Life Sciences opened a new HPAPI manufacturing facility at its cGMP API manufacturing campus in Bidar, India. The new 16,000-square-foot HPAPI facility can handle HPAPIs with less than 1 μg/m3 containment. Earlier in 2022, the company opened an HPAPI development facility at its Hyderabad, India, R&D campus.
Procos, a Cameri, Italy-based CDMO, is investing EUR 17 million ($19 million) to expand its existing HPAPI manufacturing facility by adding two new cGMP small-scale and milling units. After several successful years of involvement in the HPAPI business, which started in 2018, the company invested an additional EUR 17 million ($19 million) to create more capacity for the containment level with an occupational exposure limit of 10ng/m3 and to add new technologies in this area, such as chromatographic purification, nanofiltration systems, and freeze dryers.
Seqens is proceeding with an expansion at the company’s site in Aramon, France, to build a new multi-tonnage production line for HPAPIs. The EUR-26 million ($28-million) investment will allow this new unit to deliver 10 T/year of HPAPIs. Completion was scheduled for the end of 2023.
Siegfried is adding to its small-molecule API capacity through the addition of a new large-scale production plant in Minden, Germany, with a total investment of up to CHF 100 million ($109 million), slated to be operational in 2024. The company is also adding a new R&D Center for Drug Substances in Evionnaz, Switzerland.
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.
Euroapi is investing EUR 50 million ($54 million) to expand prostaglandin manufacturing capacity at its site in Budapest, Hungary. The expansion involves debottlenecking and the installation of new manufacturing equipment that will more than double overall prostaglandin capacity of the company’s Budapest site. The expansion is slated to be completed by 2027 in two phases: 2023-2025 (approximately two-thirds of the total investment) and 2026-2027 (the remaining one-third of the investment).
Seqens is investing nearly CNY 300 million ($43 million) in three new production capacity projects in China. These three projects will complement Seqens’ industrial facilities and investments in Europe and support products for the healthcare and cosmetics markets.
In 2023, Olon announced a EUR 10-million ($10.7-million) multi-year expansion plan for its production site in Mahad, India. The expansion will increase the plant’s total production capacity by 45% in chemical synthesis. The new production line will include reactors and filter dryers equipped with all necessary utilities, and will come into operation in the second quarter of 2024, allowing for gradual further capacity growth until 2026.
In 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 was 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 invested 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 was slated to come on line in late 2022 and mid-2023, respectively. A $30-million expansion in its High Point, North Carolina, facility approximately doubles 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 gives Cambrex the ability to develop and manufacture HPAPIs at the facility.
PharmaBlock is investing $90 million to expand its drug-substance manufacturing facility in Zhejiang, China. The facility added two new GMP workshops, including a continuous manufacturing area in 2022, and another GMP workshop was slated to open in 2023. In addition, PharmaBlock USA opened a new campus in West Chester, Pennsylvania, in March 2023. This $13-million investment enhances PharmaBlock’s capabilities in developing and supplying clinical-stage APIs in the US.
Also in 2023, Axplora installed a new cGMP pilot unit for flow chemistry at its Leverkusen, Germany, site. The equipment allows Axplora to operate at a broad range of temperatures and pressures (-50° C up to 200° C and up to 40 bar), with reactor configurations adapted to the specific requirements of the process.
Also in 2023, Macfarlan Smith, a subsidiary of Veranova (formerly known as Johnson Matthey Health), completed a $10-million expansion of mid-scale API manufacturing capacity at its facility in Edinburgh, Scotland. The $10-million expansion is one of two recent investments; the two expansions represent $17 million in investments.
Note: currency conversions are as of the time of announcement.