Tim Wright, Editor, Contract Pharma03.11.22
Oral solids are cost-effective, easy to manufacture and patient-friendly, making them the most common dosage form in the pharmaceutical industry. In addition, advances in drug delivery technology, such as targeted drug delivery and sustained release dosage forms, are enabling oral solids to achieve even greater levels of bioavailability while reducing the frequency of drug administration. Other benefits exist in terms of relatively uncomplicated packaging needs and storage and distribution requirements due to chemical and physical stability.
As the most preferred drug delivery form, oral solids are used across a wide spectrum of the pharmaceutical landscape. In fact, the small molecule outsourcing market is expected to reach $69.4 billion by 2024, with the demand being driven by complex molecules, according to Visiongain’s report, “Pharmaceutical Contract Manufacturing Market 2019-2029.”
Over the past several months, contract development and manufacturing organizations (CDMOs) have continued to invest in and expand their oral solid dosage (OSD) development and manufacturing capabilities to meet the growing demands of the market. Some recent and notable examples follow.
CordenPharma Acquires Three GMP Manufacturing Facilities
CordenPharma, a full-service CDMO supplying APIs, excipients, drug products and associated packaging services, has completed the acquisition of three manufacturing facilities from Vifor Pharma, to be ultimately renamed Corden Pharma Fribourg S.A. (including its Ettingen branch) in Switzerland, and Corden Pharma Lisbon S.A. in Portugal.
The acquisition of the Vifor Pharma manufacturing sites expands CordenPharma’s capabilities and capacities in the manufacturing of non-sterile drug product dosage forms, including but not limited to, OSD forms such as tablets and capsules. With the addition of these three new facilities, CordenPharma’s global network now consists of 12 locations (11 GMP sites and one R&D laboratory), supported by more than 2,600 employees generating expected sales of over €800 million in 2022.
Catalent Launches Xpress Pharmaceutics Service
Catalent recently launched its new Xpress Pharmaceutics service, designed to accelerate the development of oral drugs through Phase 1 clinical studies. By integrating formulation development, on-demand clinical manufacturing, regulatory support and clinical testing, the approach can reduce both the cost and time taken to complete first-in-human trials, according to the CDMO.
Xpress Pharmaceutics allows Catalent to work alongside innovator and clinical research organizations (CROs), and provide formulated clinical trial material with the necessary stability data that can be prepared for dosing patients at the clinical site, in line with adaptive study protocols. This approach provides a faster alternative to the traditional clinical development model, and offers the advantage of flexible dose and/or formulation composition adjustment during a clinical trial, guided by real-time clinical data.
The service will be delivered by formulation development experts at Catalent’s facilities in Nottingham, UK and Beinheim, France and supported by the company’s global regulatory affairs team. To further support accelerated timelines, Catalent has a pre-qualified CRO partner, allowing seamless transition from manufacturing into clinical testing.
Procaps Acquires First U.S. Softgel Production Facility
Barranquilla, Colombia-based Procaps Group, an integrated international healthcare and pharmaceutical company, closed an asset purchase agreement to acquire an 86,000 square foot pharmaceutical production facility located in West Palm Beach, FL with production capacity of approximately 1.8 billion capsules per year for its iCDMO (integrated contract development and manufacturing organization) business unit, and is expected to increase the company’s product development capabilities by more than 70%.
The soft gelatin capsule is a solid dosage form composed of two gelatin films that contain semisolid or liquid APIs protected by an external, hermetically sealed cover. Softgels are designed to deliver high precision dosage by achieving homogeneity of ingredients. The softgel capsules are well recognized in the supplement, over-the-counter (OTC) and the prescription market for improving patient adherence to the drug and therapy by facilitating swallowing due to the texture of its shell.
The pharmaceutical production facility was purchased from Strides Pharma, a U.S. subsidiary of the Indian-based pharmaceutical corporation, the Strides Group. The facility is U.S. FDA approved and, in addition to the manufacturing capabilities, it offers development and analytical testing capacities, which the company says will become an important alternative for new pharmaceutical and OTC developments in highly regulated markets worldwide. Core assets included in the acquisition were several softgel encapsulation lines, new critical support systems, automated packaging line capabilities, as well as development facilities including pilot and scale up capabilities. Procaps Group expects the facility to begin operations in May of 2022.
Eurofins CDMO Expands Spray Drying Capabilities
Eurofins CDMO is expanding its spray dry development and production services in North America. The Canadian facility, located in Mississauga, Ontario, has expanded its cGMP spray drying capabilities with the addition of a GEA Mobile Minor spray drying system and dedicated 500 square foot clean room.
With this expansion, Eurofins CDMO can further complement a broad range of services specializing in solubility enhancement for clinical development and small-scale commercial programs. Its process capabilities include solvent or aqueous systems, highly potent compounds, API and drug product development and manufacturing, solid state characterization, oral solid and inhalation dosage forms.
The expansion of spray drying at Eurofins CDMO provides continued support of clinical development programs where formulation enabling is required for poorly soluble compounds. The new spray dry system enables manufacturing of solid dispersions at multi-kilo scale in support of a wide range of finished dosage forms for early clinical through to niche commercial programs.
Piramal Strengthens North American Capabilities
The CDMO Piramal Pharma Solutions has recently added development- and commercial-scale roller compaction technology to its Sellersville, PA drug product facility. The addition of the Gerteis Macro-pactor equipment, which is designed to handle both development and commercial scale roller compaction, enhances the site’s dry granulation and scale-up capabilities.
Piramal Pharma solutions enhances solid oral dosage formulation capabilities in North America with the Gerteis Macro-pactor, known as the market leader in roller compaction technology.
Market data indicates that more than 20% of the new chemical entities being developed use roller compaction technology in their development and/or commercialization. In addition, roller compaction is an excellent technology for processing certain APIs, according to the company. The densification of dry blended powders is a critical capability that is required to handle products with poor API flow properties and instances where the API is moisture sensitive. Wet granulation is sometimes used to overcome these challenges, but many APIs are not amenable to wet granulation. In such cases, roller compaction provides a viable option to densify material and generate granules which can be further processed into capsules or tablets.
The Gerteis Macro-pactor is a versatile piece of equipment, with the ability to handle 100-300 gram batches for small-scale development as well as larger volumes when used in continuous mode. It is recognized as an effective solution for both small-scale development requiring roller compaction technology and larger scale clinical and commercial batches as the compounds move forward in the development cycle.
New CDMO Astrea Pharma Buys Recipharm Site
A newly established CDMO, Astrea Pharma, focused on small molecule oral solid dosage forms, recently purchased Recipharm’s solid dose manufacturing site at Fontaine-lès-Dijon, France. Under Recipharm’s ownership, Fontaine has developed extensive experience manufacturing and packaging tablets and capsules. The capabilities fit well with Astrea’s ambitions to grow a broad range of different processing, filling and packaging technologies, as well as a wide geographical reach.
Astrea’s owners are veterans in the CDMO industry and have the financial backing of the French long-term investment company Groupe Chevrillon, a family-owned business with a strong track record of investment in industrial and service companies.
Metrics Contract Services Adds New Equipment
Metrics Contract Services, the contract pharmaceutical development and manufacturing division of Mayne Pharma, has invested in additional equipment to enhance capacity in early phase drug development. Another Xcelodose 600S precision powder micro-dosing system will further provide capacity and efficiency improvements in meeting increasing demand for preclinical and early phase clinical GMP supply.
Metrics’ new Xcelodose 600S is a strategic addition for Metrics’ formulation development team. The 600S can dispense dose weights as low as 100 micrograms, allowing for precise, accurate and repeated filling of capsules and other small dose containers without excipients or bulking agents. Most formulated products can also be filled without segregation. Metrics will install the new Xcelodose 600S in its state-of-the-art facility in Greenville, NC.
Hovione Enters Dispersome Technology Partnership
Hovione, a CDMO and provider of spray drying and particle engineering services, has entered a partnership with Zerion Pharma to market and commercialize Dispersome, Zerion´s proprietary solubility enhancement technology platform.
Zerion’s technology builds on a new concept of increasing drug solubility by using natural protein-based excipients to formulate APIs into amorphous solid dispersions by spray drying. By combining Dispersome technology with Hovione’s spray drying capabilities, experience in development, scale-up and GMP manufacturing, the CDMO has strengthened its position in amorphous solid dispersions, coming up with innovative solutions to overcome a prevalent challenge faced by the industry: low drug solubility.
Collaboration aims to further develop the Xelum platform and tap its potential more quickly.
Syntegon Pharma Technology, a supplier of process technology and packaging solutions for the pharmaceutical industry, has entered a strategic partnership with Bayer for the development of new continuous manufacturing processes for oral solid dosage (OSD) forms.
The cooperation is based on the Xelum platform developed by the Syntegon subsidiary Hüttlin, which the partners intend to advance together and establish as a standard in the pharmaceuti-cal industry.
Its main advantage and a novelty in continuous pharmaceutical production is the previously un-attained precise dosing of active ingredients. At the same time, fluid bed granulation provides granules with outstanding properties.
Tapping the potential of the Xelum platform
Fluid bed granulation remains the most flexible technology for the production of solid oral drug formulations. It is well established and the ease of transfer from the currently predominant batch process to continuous production is of high value to pharmaceutical companies. Continu-ous manufacturing makes it possible to further increase quality assurance in production and make new drugs available to patients faster.
Uwe Harbauer, head of Syntegon’s pharma business unit, said, “Together with Bayer, we will continue to develop our Xelum platform and tap its potential more quickly. This will enable us to align our technology even more closely with specific customer requirements. The goal is to realize a continuous line that covers all steps from powder to coated tablet.”
A unique approach to continuous manufacturing
While other continuous processes rely on screw granulation, Syntegon's Xelum platform uses fluid bed granulation, which has been well established for decades. Since granulation and dry-ing take place in the same process room, there is no need to transport wet granules. The sys-tem doses, mixes and granulates defined sub-quantities of the product, so-called X-Keys, which continuously run through the process chain and are removed from the system successively. The X-keys ensure the traceability of the ingredients, which is essential for pharmaceutical produc-tion, at all times. Xelum requires neither technology transfer nor scale-up. Product develop-ment and manufacturing are carried out according to the same principles and recipes.
In addition to further developing the Xelum platform, Syntegon's main goal is to fulfill the so-called “continuous promise,” according to Harbauer. “We want our systems to enable higher quality assurance at lower development costs,” he said. “In combination with higher flexibility in batch sizes and technology, this gives us a very positive outlook for the continuous future.”
As the most preferred drug delivery form, oral solids are used across a wide spectrum of the pharmaceutical landscape. In fact, the small molecule outsourcing market is expected to reach $69.4 billion by 2024, with the demand being driven by complex molecules, according to Visiongain’s report, “Pharmaceutical Contract Manufacturing Market 2019-2029.”
Over the past several months, contract development and manufacturing organizations (CDMOs) have continued to invest in and expand their oral solid dosage (OSD) development and manufacturing capabilities to meet the growing demands of the market. Some recent and notable examples follow.
CordenPharma Acquires Three GMP Manufacturing Facilities
CordenPharma, a full-service CDMO supplying APIs, excipients, drug products and associated packaging services, has completed the acquisition of three manufacturing facilities from Vifor Pharma, to be ultimately renamed Corden Pharma Fribourg S.A. (including its Ettingen branch) in Switzerland, and Corden Pharma Lisbon S.A. in Portugal.
The acquisition of the Vifor Pharma manufacturing sites expands CordenPharma’s capabilities and capacities in the manufacturing of non-sterile drug product dosage forms, including but not limited to, OSD forms such as tablets and capsules. With the addition of these three new facilities, CordenPharma’s global network now consists of 12 locations (11 GMP sites and one R&D laboratory), supported by more than 2,600 employees generating expected sales of over €800 million in 2022.
Catalent Launches Xpress Pharmaceutics Service
Catalent recently launched its new Xpress Pharmaceutics service, designed to accelerate the development of oral drugs through Phase 1 clinical studies. By integrating formulation development, on-demand clinical manufacturing, regulatory support and clinical testing, the approach can reduce both the cost and time taken to complete first-in-human trials, according to the CDMO.
Xpress Pharmaceutics allows Catalent to work alongside innovator and clinical research organizations (CROs), and provide formulated clinical trial material with the necessary stability data that can be prepared for dosing patients at the clinical site, in line with adaptive study protocols. This approach provides a faster alternative to the traditional clinical development model, and offers the advantage of flexible dose and/or formulation composition adjustment during a clinical trial, guided by real-time clinical data.
The service will be delivered by formulation development experts at Catalent’s facilities in Nottingham, UK and Beinheim, France and supported by the company’s global regulatory affairs team. To further support accelerated timelines, Catalent has a pre-qualified CRO partner, allowing seamless transition from manufacturing into clinical testing.
Procaps Acquires First U.S. Softgel Production Facility
Barranquilla, Colombia-based Procaps Group, an integrated international healthcare and pharmaceutical company, closed an asset purchase agreement to acquire an 86,000 square foot pharmaceutical production facility located in West Palm Beach, FL with production capacity of approximately 1.8 billion capsules per year for its iCDMO (integrated contract development and manufacturing organization) business unit, and is expected to increase the company’s product development capabilities by more than 70%.
The soft gelatin capsule is a solid dosage form composed of two gelatin films that contain semisolid or liquid APIs protected by an external, hermetically sealed cover. Softgels are designed to deliver high precision dosage by achieving homogeneity of ingredients. The softgel capsules are well recognized in the supplement, over-the-counter (OTC) and the prescription market for improving patient adherence to the drug and therapy by facilitating swallowing due to the texture of its shell.
The pharmaceutical production facility was purchased from Strides Pharma, a U.S. subsidiary of the Indian-based pharmaceutical corporation, the Strides Group. The facility is U.S. FDA approved and, in addition to the manufacturing capabilities, it offers development and analytical testing capacities, which the company says will become an important alternative for new pharmaceutical and OTC developments in highly regulated markets worldwide. Core assets included in the acquisition were several softgel encapsulation lines, new critical support systems, automated packaging line capabilities, as well as development facilities including pilot and scale up capabilities. Procaps Group expects the facility to begin operations in May of 2022.
Eurofins CDMO Expands Spray Drying Capabilities
Eurofins CDMO is expanding its spray dry development and production services in North America. The Canadian facility, located in Mississauga, Ontario, has expanded its cGMP spray drying capabilities with the addition of a GEA Mobile Minor spray drying system and dedicated 500 square foot clean room.
With this expansion, Eurofins CDMO can further complement a broad range of services specializing in solubility enhancement for clinical development and small-scale commercial programs. Its process capabilities include solvent or aqueous systems, highly potent compounds, API and drug product development and manufacturing, solid state characterization, oral solid and inhalation dosage forms.
The expansion of spray drying at Eurofins CDMO provides continued support of clinical development programs where formulation enabling is required for poorly soluble compounds. The new spray dry system enables manufacturing of solid dispersions at multi-kilo scale in support of a wide range of finished dosage forms for early clinical through to niche commercial programs.
Piramal Strengthens North American Capabilities
The CDMO Piramal Pharma Solutions has recently added development- and commercial-scale roller compaction technology to its Sellersville, PA drug product facility. The addition of the Gerteis Macro-pactor equipment, which is designed to handle both development and commercial scale roller compaction, enhances the site’s dry granulation and scale-up capabilities.
Piramal Pharma solutions enhances solid oral dosage formulation capabilities in North America with the Gerteis Macro-pactor, known as the market leader in roller compaction technology.
Market data indicates that more than 20% of the new chemical entities being developed use roller compaction technology in their development and/or commercialization. In addition, roller compaction is an excellent technology for processing certain APIs, according to the company. The densification of dry blended powders is a critical capability that is required to handle products with poor API flow properties and instances where the API is moisture sensitive. Wet granulation is sometimes used to overcome these challenges, but many APIs are not amenable to wet granulation. In such cases, roller compaction provides a viable option to densify material and generate granules which can be further processed into capsules or tablets.
The Gerteis Macro-pactor is a versatile piece of equipment, with the ability to handle 100-300 gram batches for small-scale development as well as larger volumes when used in continuous mode. It is recognized as an effective solution for both small-scale development requiring roller compaction technology and larger scale clinical and commercial batches as the compounds move forward in the development cycle.
New CDMO Astrea Pharma Buys Recipharm Site
A newly established CDMO, Astrea Pharma, focused on small molecule oral solid dosage forms, recently purchased Recipharm’s solid dose manufacturing site at Fontaine-lès-Dijon, France. Under Recipharm’s ownership, Fontaine has developed extensive experience manufacturing and packaging tablets and capsules. The capabilities fit well with Astrea’s ambitions to grow a broad range of different processing, filling and packaging technologies, as well as a wide geographical reach.
Astrea’s owners are veterans in the CDMO industry and have the financial backing of the French long-term investment company Groupe Chevrillon, a family-owned business with a strong track record of investment in industrial and service companies.
Metrics Contract Services Adds New Equipment
Metrics Contract Services, the contract pharmaceutical development and manufacturing division of Mayne Pharma, has invested in additional equipment to enhance capacity in early phase drug development. Another Xcelodose 600S precision powder micro-dosing system will further provide capacity and efficiency improvements in meeting increasing demand for preclinical and early phase clinical GMP supply.
Metrics’ new Xcelodose 600S is a strategic addition for Metrics’ formulation development team. The 600S can dispense dose weights as low as 100 micrograms, allowing for precise, accurate and repeated filling of capsules and other small dose containers without excipients or bulking agents. Most formulated products can also be filled without segregation. Metrics will install the new Xcelodose 600S in its state-of-the-art facility in Greenville, NC.
Hovione Enters Dispersome Technology Partnership
Hovione, a CDMO and provider of spray drying and particle engineering services, has entered a partnership with Zerion Pharma to market and commercialize Dispersome, Zerion´s proprietary solubility enhancement technology platform.
Zerion’s technology builds on a new concept of increasing drug solubility by using natural protein-based excipients to formulate APIs into amorphous solid dispersions by spray drying. By combining Dispersome technology with Hovione’s spray drying capabilities, experience in development, scale-up and GMP manufacturing, the CDMO has strengthened its position in amorphous solid dispersions, coming up with innovative solutions to overcome a prevalent challenge faced by the industry: low drug solubility.
Collaboration aims to further develop the Xelum platform and tap its potential more quickly.
Syntegon Pharma Technology, a supplier of process technology and packaging solutions for the pharmaceutical industry, has entered a strategic partnership with Bayer for the development of new continuous manufacturing processes for oral solid dosage (OSD) forms.
The cooperation is based on the Xelum platform developed by the Syntegon subsidiary Hüttlin, which the partners intend to advance together and establish as a standard in the pharmaceuti-cal industry.
Its main advantage and a novelty in continuous pharmaceutical production is the previously un-attained precise dosing of active ingredients. At the same time, fluid bed granulation provides granules with outstanding properties.
Tapping the potential of the Xelum platform
Fluid bed granulation remains the most flexible technology for the production of solid oral drug formulations. It is well established and the ease of transfer from the currently predominant batch process to continuous production is of high value to pharmaceutical companies. Continu-ous manufacturing makes it possible to further increase quality assurance in production and make new drugs available to patients faster.
Uwe Harbauer, head of Syntegon’s pharma business unit, said, “Together with Bayer, we will continue to develop our Xelum platform and tap its potential more quickly. This will enable us to align our technology even more closely with specific customer requirements. The goal is to realize a continuous line that covers all steps from powder to coated tablet.”
A unique approach to continuous manufacturing
While other continuous processes rely on screw granulation, Syntegon's Xelum platform uses fluid bed granulation, which has been well established for decades. Since granulation and dry-ing take place in the same process room, there is no need to transport wet granules. The sys-tem doses, mixes and granulates defined sub-quantities of the product, so-called X-Keys, which continuously run through the process chain and are removed from the system successively. The X-keys ensure the traceability of the ingredients, which is essential for pharmaceutical produc-tion, at all times. Xelum requires neither technology transfer nor scale-up. Product develop-ment and manufacturing are carried out according to the same principles and recipes.
In addition to further developing the Xelum platform, Syntegon's main goal is to fulfill the so-called “continuous promise,” according to Harbauer. “We want our systems to enable higher quality assurance at lower development costs,” he said. “In combination with higher flexibility in batch sizes and technology, this gives us a very positive outlook for the continuous future.”
