By the numbers, oral solid dosage (OSD) products remain the largest segment of the pharmaceutical market. The global OSD pharmaceutical formulation market is forecasted to grow from $493 billion in 2017 to $926 billion by the end of 2027, according to Future Market Insights. This represents a compound annual growth rate (CAGR) of 6.5% over the 10-year forecast period.
In terms of New Molecular Entities (NMEs), from 2015-19, between 70% and 80% of NMEs approved by the FDA were small molecules. In 2019, 68% of the small molecules approved were delivered through oral dosages.
“The current state of oral solid dose manufacturing is both mature—in that conventional tablet formulations and capacity exist—and immature—in that new formulation capabilities need to be developed and improved for more complex problem statements like bioavailability enhancing technologies and patient centric dosage forms like pediatric controlled release products,” said Dan Dobry, head of drug product commercial development, Lonza Pharma & Biotech.
OSD Growth Trends
Perhaps the greatest impact on the OSD market has been the growth in the oncology sector. Between 2015 and 2020, clinical-stage cancer programs increased by 77% (1,642 to 2,911) and continue to dominate the landscape, which has led to roughly one-quarter of drugs currently in development worldwide being categorized as highly potent.
This trend toward high potency is having a notable impact on the contract development and manufacturing organization (CDMO) space as the growing need for smaller scale and contained manufacturing processes poses a challenge for much of pharma’s installed capacity.
“Many companies with candidates in these areas do not have the facilities needed to take a product from development to market, which is driving outsourcing to specialist CDMOs,” said John Ross, president at Mayne Pharma U.S. and Metrics Contract Services. “Larger contract manufacturers often sell higher production volumes and multi-site capabilities, but the trend has been towards specialist CDMOs as they often offer better continuity from development through to commercial requirements. Depth of specific expertise in applicable technologies is also imperative as it can often accelerate timelines and provide higher quality outcomes. This is critical in a market where getting it right quickly is typically far more valuable to sponsors than saving money on a per line item basis.”
Another key trend affecting the global oral solid dose market is the rise of useability and patient compliance as a key concern for drug developers. This increasingly patient-centric approach is fueling a rapid rise in demand for modified release (MR) oral solid dose products.
“Developers are turning to MR technology to meet their useability goals for a number of reasons,” said Torkel Gren, senior director, technology officer and strategic investments, Recipharm. “It can be used to extend the period of time that a medicine remains active in the body by maintaining therapeutic blood concentrations for longer than traditional immediate release products. It can delay action until a drug has reached a specific area, such as the small intestine, through the use of special coatings. And, it can also be harnessed to create fixed dose combinations, multi-API products, with the doses of each API designed to be released at different rates.”
These features offer huge benefits for patients. “They can enhance the therapeutic effect of a drug and can potentially reduce adverse side effects by delaying activity until it reaches the target area and lowering plasma peak concentration while maintaining the desired therapeutic effect,” continued Gren. “Most importantly, they can reduce the number of daily doses required, making them more user-friendly and enhancing patient compliance. These patient-centric benefits can help oral solid dose products maintain market share when compared with rival dosage forms.”
Moving forward, amorphous solid dispersion technology will only become more sophisticated in addressing the pervasive challenge of poor bioavailability.
According to Lonza’s Dobry, the utility of spray drying technology has been expanded through processing innovations to address highly insoluble molecules using a superheated feed system that makes many previously undruggable candidates viable as amorphous solid dispersions.
In addition, Dobry said a significant new development in oral solid drug delivery technology is a lipid multi-particulate (LMP) platform aimed at tunable release and enablement of a range of patient centric dosage forms.
“In this technology,” he explained, “the drug is encapsulated in a molten lipid mixture that is atomized on a spinning disk and congealed prior to collection. This technology produces 100-300 micron spherical particles with good mouth feel. The product can be encapsulated for adult populations but can also be used for pediatric and geriatric populations due to ease of swallowability. Because this process is semi-continuous, it allows for LMPs to be used in early clinical trials and into the commercial phase with a common process scale. In addition to tuning the lipid excipients for function, the LMPs can be coated for delayed release or taste-masking applications.”
Over the past year, CDMOs have continued to invest in and expand their OSD development and manufacturing capabilities to meet the growing demands of the market. Some recent and notable examples follow.
Lonza and NextPharma. In January 2021 the two companies entered an agreement for the potential sale of Lonza’s Ploermel, France and Edinburgh, U.K. sites, which produce liquid-filled hard capsules, including Licaps, and softgels for high potent and hormonal products. With this intended divestment, Lonza plans to exit both softgels and liquid-filled hard capsules for the pharma market, aside from retaining capability for feasibility studies as part of a technology selection offering. In the consumer health and nutrition space, Lonza plans to exit softgels but continue to offer Licaps-based products (lipid capsules) out of Colmar (FR), Greenwood (US) and Sagamihara (JP). Capsules, including Licaps for nutrition, remain core to Lonza’s offering and the company has recently announced an investment of $93 million to expand capsule manufacturing capacity by 30 billion capsules annually across eight sites.
With this intended acquisition, NextPharma plans to develop and broaden its technology offering into lipid-based finished dosage forms—softgels and liquid-filled hard capsules—in addition to offering high potency capabilities and New Chemical Entity (NCE) development services. In 2020 the London-headquartered CDMO completed a $17 million investment to expand its existing capacity for manufacturing and packaging of oral solid dosage forms at its site in Goettingen, Germany. The project involved construction of a new 1,000-square-meter building on two levels, with additional production facilities on the ground floor for mixing, compression, film coating, and granulation. The expansion increased capacity at the site by 25%, equivalent to an increase in manufacturing and packaging capacity of approximately 1 billion tablets. A packaging line for blister packs was installed on the upper floor of the building, and another bottle packaging line will be added in the second quarter of 2021.
More recently, Lonza expanded its solid form selection services based at its Bend, OR site. The added capabilities build on the SimpliFiH Solutions first-in-human services consisting of phase-appropriate drug substance and drug product development and manufacture. The solid form services offering also enhances Lonza’s capabilities to meet accelerated timelines for increasingly complex molecules.
Metrics Contract Services. The CDMO started construction on the expansion of its novel oral solid dosage manufacturing facility expansion in Greenville, NC. The $10 million investment will add 3,760 square feet of production space to the current facility, providing added flexibility and capacity to the CDMO and its clients. The expansion consists of three new rooms: one dispensing/flex room, one tablet press room, and one flex room to accommodate the company’s growing portfolio of commercial services following sustained increase in demand from clients for high potent handling capabilities. New equipment also forms part of the investment and includes a Fette FE55 tablet press, a Bosch 720 encapsulator, which both offer containment capabilities for the safe handling of potent products, and a weigh and dispense isolator.
CoreRx. The CDMO opened its fourth new facility, on the ICOT campus in Clearwater, FL in August 2020. The new Product Development Center includes nine R&D formulation development and R&D-scale manufacturing suites, nearly 5,000 square feet of analytical laboratory space as well as capacity for an additional 35 employees. The new 26,000 square foot space expands the capacity of CoreRx’s oral and topical dosage form development group, increasing drug product volume through several formulation technologies that include: blending, roller compaction, wet granulation, fluid bed drying, spray drying, and extrusion spheronization. This expansion gives CoreRx’s clients access to over 150,000 square feet of space at the ICOT center campus. The new facility is designed to streamline workflow and optimize product development efficiency, with analytical development, pre-formulation, and formulation development teams all collocated for optimal synergy.
Catalent. In August 2020 Catalent unveiled plans to expand its Argentinian site in Loma Hermosa, Buenos Aires, adding more than 11,000 square feet of production space segregated and designed to handle cytotoxic and highly active products for prescription softgel manufacturing. The new facilities, scheduled to be completed in December 2021, will include two new manufacturing vessels of 40 and 300 liters, which include an automatic cleaning system and an innovative mixing device suitable for very high viscosity formulations, a capsule filling line and six drying tunnels. This will add a capacity of over 10 million doses per year to the site, which supplies products to the Latin American, U.S., and European markets.
In other news, in June 2020 Catalent completed a $3.2 million expansion program at its consumer health manufacturing facilities in Strathroy, Canada and Sorocaba, Brazil. The expansion projects include new softgel encapsulation lines at each site, dedicated to Catalent’s Vegicaps plant-based capsule and CosmoPod twist-off capsule technologies. The increased capacity will enable Catalent to support its customers in both North and Latin America to develop products for consumers seeking all-natural and plant-based vitamins, minerals and supplements, using its Vegicaps capsule; and those looking for innovative, easy-to-use, unit-dose beauty care products, through its CosmoPod technology.
Adare Pharmaceuticals. The clinical-stage pharmaceutical company and global provider of advanced pharmaceutical technologies acquired Orbis Biosciences of Lenexa, KS. Orbis provides enhanced technologies in a scaled, single-step manufacturing process. Its Precision Particle Fabrication technology is capable of producing uniform particles in size ranges suitable for use in injectable and oral dosage forms. Adare’s technologies include: Microcaps for taste-masking via a solvent or aqueous based coacervation process; Diffucaps that incorporates release-controlling polymers or protective coatings onto drug-layered cores, granules, or crystals; and the MMTS Multi Mini Tablet System in which functional membranes are applied to 1.0-2.0 mm cylindrical tablets to control release rates.
ACG. Pharma/nutra manufacturing solutions provider ACG recently added another specialist division to its integrated global offering with the official inauguration of its first ACG Laboratories site—a lab for process development in Shirwal, India. The new facility is set to provide ACG’s customers and partners with a research, development, testing, and training environment dedicated to the collaborative exploration of all aspects of oral solid dosage manufacturing. The lab houses a dedicated R&D space for small-scale development, and a pilot area for scale-up and process optimization studies. It is equipped to accommodate multiple projects at a time.
Alcami. In January 2021 the CDMO announced an additional $2 million investment to expand its oral solid development and manufacturing capabilities in Wilmington, NC. The investment will add a Gerteis Mini-Pactor roller compactor and low humidity suites to Alcami’s existing 140,000 square foot campus in Wilmington. The expansion, which is on track to be completed in the first and second quarter of 2021, respectively, adds dry granulation capabilities and increased flexibility to support moisture-sensitive processes.
Tim Wright is the Editor of Contract Pharma. He can be reached at TWright@RodmanMedia.com.