CDMOs/CMOs Expand High-Potency Manufacturing

By Patricia Van Arnum - DCAT Editorial Director

September 12, 2018

Oncology is the largest therapeutic sector in the global and US pharmaceutical markets with US spending on cancer drugs reaching almost $50 billion in 2017. Following that trend, CMDOs and CMOs are investing in high-potency development and manufacturing. So which companies are expanding?

Inside the oncology-drug market

Global spending on cancer therapies and supportive-care products rose to $133 billion globally in 2017, up from $96 billion in 2013, according to a recent analysis, Global Oncology Trends 2018: Innovation, Expansion and Disruption, by the IQVIA Institute for Human Data Science.

Spending on cancer drugs in the US has doubled since 2012 and reached almost $50 billion in 2017, with the lion’s share of that growth tied to drugs launched within the past five years. US spending on oncology medicines accounts for approximately 46% of global spending. Outside the US, oncology drug costs exceeded $60 billion in 2017 driven by new product launches and increased use of existing brands. Overall, spending on cancer medicines continued to be focused in the major developed markets, with the US, EU5 (France, Germany, Italy, Spain, and the UK), and Japan accounting for 74% of spending in 2017, up from 72% in 2013.

Growth rates for therapeutics—measured in constant dollars—slowed globally and across most regions in 2017 although they remained in double digits at 12.5% globally and 12.1% in the US, down from 14.8% and 17.4%, respectively, in 2016. The major factor slowing growth in the US in 2017 was a drop-in growth from new medicines following a low number of approvals in 2016 while in other markets, uptake of medicines and increased use of existing brands drove growth in 2017. Supportive care spending was almost unchanged over five years, dropping $100 million from $23.7 billion in 2013 to $23.6 billion in 2017, according to the IQVIA study. This now represents 18% of spending globally in 2017, down from 25% in 2013.

On a pipeline basis, the industry’s pipeline for oncology drugs reached an historic level of 710 molecules in late-stage development in 2017, up more than 60% from a decade ago, and with almost 90% of the therapies being targeted treatments, according to the IQVIA report. Of the 710 molecules in late-stage development, 335, or 47% are small molecules, and 301, or 45% are biologics. The remaining types are: cytotoxics (54 molecules, or 8% of the industry’s pipeline); hormonals (17 molecules, or 2% of the pipeline); and radiotherapies (three molecules, or 0.4% of the pipeline).

On a company basis, almost 700 companies or organizations have one or more oncology drugs in late-stage development, and 14 of the world’s largest pharmaceutical companies have at least one-third of their late-stage R&D activity focused on oncology, according to the IQVIA report. The group of large companies with total corporate sales above $10 billion average just under 40% of their pipeline in oncology. Companies with the greatest focus in oncology have, on average, 18 molecules in late-stage development, with an average of two indications for each drug. Of the 455 smaller companies with more than 90% of their pipeline in oncology, they are involved in 1,692 product-indications, which represents 43% of the overall cancer-drug pipeline.

CDMOs/CMOs expand in high-potency manufacturing

Biologics and newer approaches, such as immunotherapies, constitute the oncology-drug market, but small molecules, including cytotoxics, and hybrid approaches, such as antibody-drug conjugates (ADCs) are also part of the market and represent opportunities for contract development and manufacturing organizations (CDMOs) and contract manufacturing organizations (CMOs) in high-potency manufacturing of both drug substances and drug products. Some recent or announced expansions from CDMOs/CMOs in high-potency manufacturing are highlighted below.

Abzena. Earlier this year (March 2018), Abzena, a contract manufacturer of biologics and ADCs, completed a facility remodeling for a new ADC GMP manufacturing suite at its Bristol, Pennsylvania site. The facility and equipment verification and qualification for the Bristol ADC GMP manufacturing suite was scheduled for completion around the end of the second quarter of 2018. The Bristol ADC manufacturing suite adds to the company’s existing GMP manufacturing capability for the scale-up and manufacture of highly potent payload-linker constructs and the upgrading and expansion of Abzena’s biologics process development and manufacturing capabilities in San Diego, California.

AGC. AGC, a Tokyo-headquartered manufacturer of glass and chemicals, is planning an expansion of its facilities in Chiba, Japan to increase the company’s manufacturing capacity for pharmaceutical intermediates and active pharmaceutical ingredients (APIs). The new capacity, which will increase capacity at the Chiba plant by tenfold, is set to come on line in October 2019. While AGC previously mainly provided contract services for the development stage of new drugs, this expansion will give AGC the end-to-end capability to produce commercial drugs too. The new facilities will also be capable of producing highly potent APIs.

Alcami. In October 2017, Alcami, a CDMO for APIs and drug products, launched a Center of Excellence at its API development and manufacturing facility at its site in Germantown, Wisconsin. Previously announced capability extensions in controlled substances and highly potent APIs are serviced by the Center of Excellence. The company initiated process development for its first highly potent API program in the second quarter of 2017 and with plans to begin manufacturing in the fourth quarter of 2017 with a pipeline of programs to follow.

Ajinomoto Althea. Last month (August 2018), Ajinomoto Althea, a San Diego, California-headquartered contract development and manufacturing organization, opened a new antibody drug conjugate and highly potent fill/finish facility near its existing campus in San Diego. The 57,000-square-foot facility manufacturing facility includes areas dedicated to bioconjugation, formulation, purification, quality control, and sterile fill/finish including lyophilization. The facility can accommodate early clinical phase through commercially approved programs.

Cambrex. Cambrex, a CMO of small-molecule active pharmaceutical ingredients (APIs) and intermediates, is progressing a new $24-million facility for manufacturing highly potent APIs at its site in Charles City, Iowa. The project will also see the reconfiguration of the existing small-scale manufacturing area to provide a single high-containment building to support early-stage development and manufacturing. The facility is expected to be operational in the first half of 2019. The expansion is part of an ongoing strategic campaign by Cambrex to invest in small-molecule API development and manufacturing across its facilities and follows the opening of a $50-million, 7,500-square-foot multi-purpose manufacturing facility at Charles City in 2016, which added a total of 70 cubic meters of manufacturing capacity to the site.

CordenPharma. CordenPharma is a contract provider of both small-molecule APIs and drug products (including solid-dosage products and sterile injectables), acquired a former Pfizer facility, a 54,000-square-foot API manufacturing facility in Boulder, Colorado with more than 100 employees, in November 2017 to build its capabilities in high-potency manufacturing. The facility, now called CordenPharma Boulder, specializes in the development, scale-up, optimization, and production of highly potent and cytotoxic/cytostatic APIs from development quantities to commercialization. The acquisition of the Boulder facility is aligned with a broader corporate strategy of offering fully integrated supply (APIs, drug products, packaging, and logistics), including a broad range of expertise in the development and manufacturing of highly potent and oncology products. CordenPharma Boulder and CordenPharma Colorado manufacture high-potency APIs. CordenPharma Plankstadt (Germany) focuses on highly potent oral solid dosage formulations, and CordenPharma Latina (Italy) is focused on oncological injectables.

Dipharma. Earlier this year (May 2018), Dipharma, a Baranzate, Italy-headquartered API manufacturer, acquired Kalexsyn, a Kalamazoo, Michigan-headquartered contract research organization providing chemistry services, including custom synthesis, stable label synthesis, process impurity synthesis, and process route improvement. At the time of the announced acquisition in April 2018, Dipharma said it was planning to invest in Kalexsyn to add cGMP and highly potent active pharmaceutical ingredient capabilities in support of Phase I and early Phase II development. Design activities have begun with an anticipated ground-breaking later in 2018 with the facility expected to be fully operational by the fourth quarter of 2019.

Indena. Earlier this year, Indena, a Milan, Italy-headquartered CMO for the identification, development, and production of APIs derived from plants, opened a new kilolab for highly potent active pharmaceutical ingredients (natural, semisynthetic, and total synthetic) in Settala, Italy. Indena plans further investment in 2018 by building a new multi-purpose pilot plant, designed for grinding, extracting, and purifying toxic plants. It will also be equipped with columns for chromatographic purification and with semi- and total-synthesis capabilities.

Minakem.  Minakem, the CDMO division of Minafin, a Mont-Saint-Guibert, Belgium-based fine chemicals producer, has opened a new closed-controlled environment high-containment production facility at the company’s plant in Louvain-la-Neuve, Belgium. The new facility extends Minakem’s capacity to develop and manufacture highly potent APIs from small-scale development to full GMP batch releases. Operations at the new high-containment facility were scheduled to start in September 2018.

Novasep. In 2017, Novasep, a Lyon, France-headquartered CMO, opened a new EUR 11-million ($11.6-million) bioconjugation facility at its site in Le Mans, France, for clinical and commercial manufacturing of ADCs. The new facility completes Novasep’s ADC manufacturing platform, which includes ADC payloads, drug linkers, and monoclonal antibody commercial-scale production capabilities.

Piramal Pharma Solutions. Piramal Pharma Solutions, a CDMO of APIs and drug products, is investing approximately $60 million to expand API development and manufacturing capabilities, which includes extending the high-potency API capabilities at its facility in Riverview, Michigan to meet potency requirements of up to 10 ng/cubic meters. Piramal acquired the facility as part of its acquisition of Ash Stevens, a CMO of small-molecule APIs, in 2016.

Procos. Procos SpA is progressing a GMP manufacturing unit dedicated to high-potency APIs at its facility in Cameri, Italy, located near Milan. The $21-million investment, which started in the first quarter of 2016, was scheduled for completing process-validation activity in the second quarter of 2018. The 1,200-square-meter unit includes 500 square meters of production space, 500 square meters of laboratory space, and 200 square meters of warehouse/auxiliary space. The high-potency manufacturing unit is part of a larger investment and site-expansion project of $70 million that was initiated in 2014 and that was supported by Procos’ parent company, CBC Co. Ltd. Group, a privately held company based in Tokyo.

Siegfried. As part of its new “Evolve” strategy, Siegfried, which provides both small-molecule API and drug-product (solid-dosage and sterile manufacturing/aseptic filling) development and manufacturing services, says it plans to grow within the value chain of its existing businesses by reaching critical size in the drug product sector and through backward integration. Siegfried plans to diversify into adjacent new businesses by enhancing its technology base in micronization, lyophilization, spray drying, and by adding additional high-potent manufacturing capabilities.

SK biotek. Earlier this year (January 2018), SK biotek, a Seoul, South Korea-based wholly owned subsidiary of SK Holdings, set up operations at its small-molecule API manufacturing facility in Swords, Ireland, which the company had earlier acquired from Bristol-Myers Squibb. The addition of the 21-acre site adds 82 cubic meters of reactor capacity. Reactor volumes in the large-scale plants range from 4 to 7 cubic meters, and volumes in the small-scale plants range from 0.3 to 4 cubic meters of conventional space as well as 0.06 to 1.6 cubic meters for high-potency APIs. In addition, In July 2018, SK Holdings agreed to acquire Ampac Fine Chemicals (AFC), a Rancho Cordova, California-headquartered CMOs and intermediates. AFC offers several specialized technologies, including production of highly potent compounds and highly energetic compounds as well as continuous processes, and industrial-scale chromatographic separation using simulated moving bed chromatography.

Sterling Pharma Solutions. Sterling Pharma Solutions, a Dudley, UK-headquartered small-molecule API CDMO, is investing £6 million ($8 million) to expand its pilot plant at its UK site to increase capacity by 33% and enhance the site’s production capabilities for small- to mid-scale batch production. The investment will add three new reactor trains at scales of 225 liters, 500 liters and 1,360 liters to meet demand for batch sizes in the 10-100 kg range as well as add a range of new capabilities to expand the company’s ability to handle potent compounds across a range of equipment scales. The facilities, based on a 40-acre site in northeast England, were scheduled to be operational by mid-2018. Sterling Pharma Solutions launched as an independent CDMO following a management buyout of the Dudley, UK site of Shasun Pharma Solutions Dudley site in 2016.

WuXi AppTec. STA Pharmaceutical, a subsidiary of WuXi AppTec, signed an investment agreement in late April 2018 with the government of Shanghai, Jinshan District, China to build a new research & development center for APIs and intermediates located next to the company’s existing Jinshan drug-substance manufacturing site and will add more than 30,000 square meters of laboratory space and 500 scientists. The new campus will provide access to technology platforms such as flow chemistry, biocatalysis, and high-potency manufacturing from laboratory to commercial scale. The company’s current Jinshan site focuses on manufacturing APIs and advanced intermediates from kilo to metric ton scale.

In addition, earlier this year (June 2018), WuXi Biologics, part of WuXi AppTec, a Shanghai, China-headquartered contract service provider, began construction of an ADC service center in Wuxi, China. The $20-million 6,000-square-meter facility will be operational in 2019 and provide integrated services from concept to commercialization for biologics conjugates, including ADCs and other protein conjugates.