Tracking Expansions in High-Potency Manufacturing

By Patricia Van Arnum - DCAT Editorial Director

June 3, 2020

Driven by growth in oncology drugs, high-potency manufacturing is an active area of investment by CDMOs/CMOs. Which CDMOs/CMOs are making investments? DCAT Value Chain Insights rounds up key recent expansions for drug substances and drug products.

Expansions 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 CDMOs/CMOs. Several CDMOs/CMOs have made or announced expansions in high-potency manufacturing. Below are highlights of recent expansion activity.

Lonza. Last year (June 2019), Lonza announced an investment to expand highly potent active pharmaceutical ingredient (HPAPI) capacity at its site in Visp, Switzerland by adding two 4m3-scale, multi-purpose production lines for HPAPI manufacturing. The expansion complements the company’s existing production capacities from lab to large commercial scale and further involves a subsequent capacity optimization in existing production lines. The expansion, when announced in June 2019, was scheduled to come on line this July (July 2020). The company has the capabilities in place to handle HPAPI to exposure levels up to 100ng/m3 across all manufacturing scales. With recent acquisitions, Lonza also added particle engineering (micronization and spray drying) for improving bioavailability and final-drug product formulation under full containment. Additionally, specialized oral dosage forms (soft gels and liquid-filled hard capsules) for solid oral low-dose/HPAPI applications have augmented the company’s fill–finish drug product capabilities.

In addition, Lonza initiated last year (July 2019), a two-year expansion of bioconjugation capacity for ADCs at its facility in Visp. Last year, it received US Food and Drug Administration (FDA) approval for the commercial manufacture of its third ADC from the facility.

WuXi AppTec. STA Pharmaceutical, part of WuXi AppTec, opened in the first quarter of 2020 a HPAPI facility at the company’s site in Changzhou, China, its second HPAPI facility. WuXi STA’s first HPAPI facility, located at its Shanghai Jinshan site in China, supports process R&D and kilo-scale production. The newly added HPAPI facility in Changzhou includes HPAPI labs and a pilot plant (250-L–1,000-L reactors) capable of handling APIs with occupational exposure limits down to 0.05 µg/m3.

Seqens. In 2019, Seqens invested approximately $30 million for a new facility for HPAPI manufacturing in Villeneuve-La-Garenne, France, located outside of Paris. The modular unit, with initial capacity of 10–15 tons per year, further allows for future investments as customer needs evolve. The potent-compound manufacturing unit maintains a maximum level of particles in the working environment of 100 ng/m3 to allow for the production of SafeBridge Category 3 potent compounds, which is classified as molecules with occupational exposure limits (OELs) ranging from approximately 30 ng/m3 to 10 μg/m3.

Cambrex. Last year (2019), Cambrex opened a new $24-million HPAPI manufacturing facility at its site in Charles City, Iowa. The 6,000-square foot facility is part of an overall multi-year investment plan by the company in small-molecule API development and manufacturing across its facilities, which included a $50-million, 7,500-square-foot multi-purpose manufacturing facility at Charles City, which opened in 2016.

Piramal Pharma Solutions. Earlier this year (January 2020), Piramal Pharma Solutions (PPS), announced an investment of CAD$25 million ($19 million) to expand its facility in Aurora, Ontario, Canada with the addition of 10,500 square feet manufacturing space in a new wing for API manufacturing overall and including HPAPI manufacturing for producing potent compounds down to an OEL of 1 mcg/m3. It will also include filtration and drying capabilities. The expansion will further include two new reactor suites as well as a dedicated filter dryer room and a portable filter dryer. The expansion is expected to be completed and running by April 2021.

In June 2019, PPS opened a new $10-million HPAPI unit at its site in Riverview, Michigan. The new wing, consisting of two kilo labs and a quality control analytical lab, was designed to handle HPAPIs with OELs of < 1 mcg/m3 and as low as 20 ng/m3. Materials produced in this new wing are primarily at kilo-lab scales; lots of < 5 kilos can be produced in this new facility.

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 2017, which included additional capabilities in high-potency manufacturing. The facility, 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 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.

Fareva. In 2019, Fareva expanded HPAPI capabilities with the completion of a $34-million investment across two sites in Europe. The company's Excella facility in Germany expanded OEB 6 (< 0.1 µg/m3) capabilities with the completion of an analytical building, addition of jet milling with an isolator, and expansion of roller compaction for high-potency products. Fareva's La Vallée site in France completed construction and qualification of analytical and chemistry R&D Labs, pilot plant, and commercial manufacturing buildings capable of handling OEB 5 (0.1 - 1 µg/m3). This investment more than doubled Fareva's HPAPI capacity. The company provides high-potent capabilities across two sites with volumes ranging from 100 L to 4000 L for development and manufacturing of both APIs and drug products up to OEB 6 (< 0.1 µg/m3) from early phase to commercial.

Flamma. Last year (2019), Flamma acquired Teva Pharmaceuticals’ Chemical Synthesis Center in Malvern, Pennsylvania. Among the capabilities of the 40,000-square-foot facility was one cGMP highly potent API kilo lab suite with isolators (classified Band 4 by SafeBridge). Flamma has two cGMP facilities in Italy, located near Milan: Chignolo d’Isola and Isso. The Chignolo site is also where the company’s headquarters are located. Additionally, Flamma is established in China, where its 100% owned Chinese subsidiary, Flamma Honkai, operates in Dalian in the Liaoning Province.

Cerbios-Pharma. In 2019, Cerbios-Pharma, a Lugano, Switzerland-based CDMO, announced the investment of new production lines in a building dedicated to HPAPIs to enable accommodation of larger volumes and batch sizes. The expansions will accommodate SafeBridge Category 3 for batches ranging from 5 kg to 30 kg. At the time of the announcement in January 2019, completion was scheduled for the second half of 2020. Additionally, in December 2019, Cerbios announced successful SwissMedic authorization of a new cGMP bioconjugation suite for up-to commercial scale manufacturing of ADCs.

Evonik. Evonik increased its assets and added additional capacities to support the small-, medium- or large-scale production of HPAPIs at its facilities in Tippecanoe, Indiana and Hanau, Germany. The expansions, reported by the company in 2018, enables the company to run several HPAPI projects down to an exposure level of 5 ng/m3.

AGC. AGC, a Tokyo-headquartered manufacturer of glass and chemicals, expanded its facilities in 2019 in Chiba, Japan to increase the company’s manufacturing capacity for pharmaceutical intermediates and APIs, including HPAPIs.

Novasep. In 2017, Novasep 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.

Ajinomoto Bio-Pharma Services. In 2018, Ajinomoto Bio-Pharma Services opened a new ADC and highly potent fill–finish facility near its existing campus in San Diego, California. The 57,000-square-foot manufacturing facility includes areas dedicated to bioconjugation, formulation, purification, quality control, and sterile fill and finish, including lyophilization. The facility can accommodate early clinical phase through commercially approved programs. In addition, the company announced last year (March 2019) further investment for the reconfiguration of GMP manufacturing suites in Belgium to support increased HPAPI capacity and improve process safety with additional instrumentation.

BSP Pharmaceuticals. BSP Pharmaceuticals, a Latina Scalo, Italy-based CDMO of oral solid dosage forms and injectables, announced in 2019 an expansion of high-containment capacity dedicated to oncology compounds and the addition of new capacity for innovative molecules and immunotherapies. The investment involves expansion of the company’s existing facilities for oncology products and cytotoxics by approximately 30,000 square feet to increase its total conjugation capacity for ADCs. The investment in high-potency manufacturing is part of additional investments announced by the company, which included the expansion of injectable drug-product capacity, additional capacity to support production of immunotherapies, and the addition of a new development laboratory for analytical, formulation and process development for conjugation and drug products (injectables and oral solids). The new capacities, as announced in 2019, are scheduled to be completed by the end of 2020.

PCI Pharma Services. PCI Pharma Services completed late last year (December 2019) an expansion of its Rockford, Illinois facility to include 30,000-plus square feet dedicated to specialty drug-product capabilities with four high-potent compound suites and three new secondary packaging areas.

Recro Gainesville. In 2018, Recro Gainesville, a CDMO of oral solid dosage products, added a 24,000-square-foot facility, which included high-potent material processing space, near its existing 97,000-square-foot contract pharmaceutical development and manufacturing plant in Gainesville, Georgia.

The expansion provides capabilities from formulation development to clinical-trial material supply to commercial manufacturing with clinical packaging capabilities to be added in 2020.The existing Gainesville site provides oral solid-dosage formulation development, regulatory support, clinical and commercial manufacturing, and packaging and logistics services to the global pharmaceutical market.

Sterling Pharma Solutions. Sterling Pharma Solutions, a Dudley, UK-headquartered CDMO of APIs, opened a pilot-plant facility in 2019 following a £6-million ($7.6-million) investment to increase API capabilities, including the handling of potent compounds. Overall, the expansion included three new reactor trains at scales of 225 L, 500 L and 1,360 L and enables small to mid-scale clinical supply and commercial batch production.

Heraeus. Heraeus Pharmaceutical Ingredients, part of Heraeus, a Hanau, Germany-based technology group, announced last year (2019) that it is expanding its production capacities for platinum-based HPAPIs.

Minakem. Minakem, the CDMO division of Minafin, a Mont-Saint-Guibert, Belgium-based fine chemicals producer, opened in 2018 a new closed-controlled environment high-containment HPAPI 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.

Procos. Procos SpA expanded to add a HPAPI manufacturing unit at its facility in Cameri, Italy, located near Milan. The expansion, which started in 2016, was completed in 2018.

Editor's Note: This article was updated to include additional information on Fareva.