Solid-Dosage Mfg: CDMO Market and Product Trends
Solid dosage products are a mainstay, but how are they faring compared to other dosage forms in terms of CDMO growth rates, product mix of new molecular entities approved thus far in 2020, and recent innovative drug approvals? DCAT Value Chain Insights takes an inside look.
New drug approvals and solid-dosage products
In looking at approvals of new molecular entities (NMEs) by the Center for Drug Evaluation and Research (CDER) of the US Food and Drug Administration (FDA) thus far in 2020 (as of October 30, 2020), 42 NMEs have been approved. Of these 42 NMEs, 17, or 40%, were solid dosage products (tablets or capsules) delivered by an oral route of administration (see Table I at end of the article), and 25, or 60%, were non-solid dosage products (i.e., no tablets and no capsules) delivered by other routes of administration (see Table II at end of the article). For purposes of the analysis of NME approvals thus far in 2020, two solution products delivered orally were included in the non-solid-dosage product category.
In looking at approvals of innovative products delivered through oral administration in 2019 in the US, the European Union (EU), and Japan, oral products accounted for between half to 42% of new product approvals. A recent analysis (1) by PharmaCircle LLC, a business intelligence firm specializing in the analysis of formulation and drug-delivery technologies and products, provides a further breakdown of recent innovative product approvals to include the following: NMEs; a new dosage form of an NME or previously approved active (PAA) or; a new combination of NME or PAA actives (note: multi-source products, generics, and biosimilars are excluded) from the US, the EU, and Japan in 2019. Based on this analysis, as was the case in 2018, oral products represented half (50%) of new product approvals in the US in 2019, according to the PharmaCircle analysis. In the EU, oral products represented 43% of new approvals in 2018 and 42% in Japan. In the EU and Japan, the number of oral and injection products were almost even in 2019: 20 oral products and 21 injection products approved in 2019 in the EU and 25 approvals each for oral and injection products in Japan. In the case of the EU, PharmaCircle notes that this is due to the regulatory approval scope by the European Medicines Agency, which approves new products and dosage form improvement for a relatively limited range of therapeutic indications.
CDMOs/CMOs: inside the numbers
Given these product trends, how are CDMOs/CMOs of solid-dosage products faring? A recent GlobalData report, Contract Dose Manufacturing Industry by the Numbers: Composition, Size, Market Share and Outlook–2020 Edition (October 2020) shows there are 602 contract manufacturing facilities worldwide that offer solid-dose manufacturing services for supply to the highly regulated markets of the US, Canada, EU, UK, and Japan. This figure includes facilities belonging to CMOs with a dedicated contract model and also pharma companies offering excess capacity contract services. (It excludes internal pharma manufacturing and CMOs manufacturing only for local, emerging pharmaceutical markets such as India.) These 602 facilities are owned by 281 CMOs. The US has 123 solid dose facilities, the EU 290 solid-dose facilities, and the UK has 29 solid-dose facilities.
On a revenue basis, solid-dose products constituted the largest proportion—43%—of contract manufacturing dose revenue for regulated markets (US, Canada, EU, UK, and Japan) in 2019, according to the GlobalData analysis. Solid-dose revenue grew by 4–5% in 2019 compared to 2018, which indicates that traditional tablet manufacture has remained relatively in demand despite overall low dose revenue growth of 3.1%. Solid dose’s growth could be driven by pharma companies’ outsourcing of less valuable generic drugs and related facilities to move non-core products away from in-house manufacturing as well as increased demand for CDMO/CMO services for more complex products, more specialized products, such as high-potency products, and increased demand for virtual or emerging pharma companies.
“Despite the pharma industry’s interest and emphasis on biologics and other molecularly complex injectables, the largest contract revenue segment for a single dosage form is still for solid-dose products,” says Adam Bradbury, Analyst, GlobalData PharmSource. “Although solid dose is a mature dosage form, oral solid-dose services for poorly soluble or modified-release products—such as tablet coating and enhanced delivery or solubility—are highly valued. Solid dose accounts for the majority of marketed products.”
CDMOs/CMOs are further benefiting from increased complexity of products and from demand from smaller or emerging pharma companies. “Small-molecule drug development is becoming increasingly innovative based on structural novelty, a sign that smaller pharma companies will require greater expertise to compete, which a CMO can provide,” says Bradbury. “Virtual pharma companies will not own manufacturing facilities and are reliant on contractors; this can only be a positive sign for CMOs. As long as virtual and small pharma companies market solid-dose products or larger pharma companies’ products become generic or non-core, contract solid dose revenue will continue to greatly contribute to the industry’s revenues for the foreseeable future,” he says.
“As drug production becomes increasingly complex from a molecular and regulatory standpoint, innovative CMOs stand to prosper,” says Fiona Barry, Associate Editor, GlobalData PharmSource. “This is especially true as the drugs pipeline favors the development of high-potency APIs for oncology, where the facilities, expertise, and equipment related to their manufacture are prohibitively expensive for smaller pharma companies, which will need to outsource. Increasing speed to market is especially important for higher value products that will end up substantially boosting revenues for a fiscal year in a pharma industry that is becoming increasingly competitive and geared towards appeasing shareholders.”
Recent facility acquisitions among solid-dose CDMOs/CMOs
In looking at the expansion activity among solid-dose CDMOs/CMOs, three recent acquisitions of facilities by solid-dose CDMOs/CMOs stand out. Earlier this year (2020), Piramal Pharma Solutions (PPS), a CDMO of APIs and drug products, acquired a solid oral dosage drug-product manufacturing facility in Sellersville, Pennsylvania from G&W Laboratories, a South Plainfield, New Jersey-based pharmaceutical company. The Sellersville site covers 31.5 acres of land with over 221,000 square feet of manufacturing space, including 195,000 square feet of GMP area, and employs a workforce of approximately 100 employees. The site features manufacturing and packaging technologies for solid oral dosage forms, liquids, creams, and ointments, quality control and microbiology labs, preformulation and analytical development infrastructure, a pilot lab for research and development, and a temperature-controlled warehouse. The site currently has the necessary controls to support manufacturing of potent solid oral dosage forms. The acquisition adds solid oral dosage-form capabilities (tablets and capsules) for PPS in North America, which until this acquisition, for PPS, were all located in the UK and India. PPS says it intends to offer high-potency drug manufacturing capabilities at the site.
In late 2019, Delpharm, a CDMO headquartered in Boulogne-Billancourt, France, announced the acquisition of five manufacturing sites in France, Canada, and the Netherlands from the Famar Group, an Athens, Greece-based CDMO. The acquisition included sites in France in Orléans (Loiret), L’Aigle (Orne), and Saint-Rémy-sur-Avre (Eure-et-Loire), Canada (Montreal), and the Netherlands (Bladel). The sites represented revenues of EUR 250 million ($294 million) and 1,300 employees.
Earlier this year (2020), Siegfried, a CDMO of APIs and drug products, agreed to acquire a site from Novartis in Barberà del Vallès, Spain, which manufactures oral solid dosage forms (OSD) and capsules used in inhalation devices. The site in Barberà del Vallès adds to Siegfried’s existing OSD capabilities in Malta by adding large-scale capacity and services to manufacture highly potent drug products and adds to its portfolio with inhalation products. The deal is expected to close by the end of 2020.
Thus far in 2020 (as of October 30, 2020), other CDMOs/CMOs are proceeding or have made recent expansions. Highlights of publicly announced deals are outlined below.
Catalent. In August (August 2020), Catalent announced plans to expand its site in Loma Hermosa, Buenos Aires, Argentina by adding over 11,000 square feet of production space to handle cytotoxic and highly active products for prescription softgel manufacturing. The new facilities, which are due to be completed in December 2021, will include two new manufacturing vessels of 40 L and 300 L, which include an automatic cleaning system and a mixing device suitable for very high viscosity formulations, a capsule-filling line, and six drying tunnels. The expansion will add capacity of over 10 million doses per annum to the site, which supplies products to Latin American, US, and European markets.
In addition, in late June (June 2020), Catalent completed a $3.2-million expansion program at its consumer health manufacturing facilities in Strathroy, Canada and Sorocaba, Brazil to include new softgel encapsulation lines at each site. The expansion projects included new softgel encapsulation lines at each site for Catalent’s proprietary Vegicaps plant-based capsule and CosmoPod twist-off capsule technologies. The increased capacity can be used for plant-based vitamins, minerals, and supplements using the company’s Vegicaps capsules and for unit-dose beauty care products through its CosmoPod technology. Catalent’s 110,000-square-foot facility in Strathroy, Ontario and its 124,600-square-foot facility in Sorocaba, Brazil provide formulation, manufacturing, and packaging services.
Lonza. Earlier last month (October 2020), Lonza announced it is investing CHF 85 million ($94 million) in its Capsules and Health Ingredients (CHI) Division to expand its overall capsule production capacity by 30 billion capsules annually across eight sites. The investment will allow a 15% increase in CHI’s current capsule production capacity. This latest commitment follows an investment initiated in 2019 to increase CHI’s capacity by 10 billion capsules. The addition of manufacturing capacity for a further 30 billion capsules will address the high growth across CHI’s gelatin, vegetarian, and specialty polymers portfolio as well as the liquid-filled hard capsules sold under the Licaps brand. The investment will be made over two fiscal years, 2020 and 2021, across eight global Lonza manufacturing sites: Bornem, Belgium; Colmar, France; Greenwood, South Carolina; Haryana, India; Jakarta, Indonesia; Puebla, Mexico; Sagamihara, Japan; and Suzhou, China.
Metrics Contract Services. In June (June 2020), Metrics Contract Services, the CDMO business of Mayne Pharma, announced an expansion of its Greenville, North Carolina, production facility to support projected growth of Mayne Pharma’s portfolio and third-party contract manufacturing business. The expansion will add 3,760 square feet of production space to the current facility and will consist of three new rooms: one dispensing/flex room, one tablet press room, and one flex room The space will house key equipment, including a Fette FE55 tablet press,a Bosch 720 encapsulator, and a weigh and dispense isolator, all which have containment capabilities for the safe handling of potent products. Construction on the production space was scheduled to begin in August (August 2020) and be operational in early 2021.
NextPharma. Earlier this year (2020), NextPharma, a London-headquartered CDMO, completed a EUR 15 million ($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 one billion tablets. A packaging line for blister packs has been installed on the upper floor of the building, and another bottle packaging line will be added in the second quarter of 2021. The building and its facilities became operational in the third quarter of 2020.
Thermo Fisher Scientific. In March (March 2020), Thermo Fisher Scientific provided an update on recent developments in its drug-product capabilities. For solid-dosage products, the company is now providing commercial spray-drying capabilities for molecules with solubility challenges. The company is also providing continuous manufacturing capabilities and new commercial packaging capabilities with smaller production runs for oral solid dosage forms.
LGM Pharma. LGM Pharma, a Boca Raton, Florida-headquartered API supplier, announced in late July (July 2020) that it had acquired the formulation development and drug-product contract manufacturing business of Nexgen Pharma, an Irvine, California-based company developing and manufacturing solid-dose, powder, semi-solid, and liquid prescription and over-the-counter drugs. The acquisition brings LGM Pharma’s knowledge in API sourcing, distribution, and supply-chain management with Nexgen Pharma’s drug-product CDMO services. The combined firm will continue to be known as LGM Pharma. With the acquisition, LGM Pharma gains Nexgen’s manufacturing and warehouse distribution facilities and employees in California and Texas along with formulation development, laboratory, and pilot-plant manufacturing employees and facilities in Colorado. In all, LGM Pharma gained 150 employees and more than 100,000 square feet of facilities along with expertise in all aspects of pharmaceutical finished-product development and manufacturing.
Frontida BioPharm. Frontida BioPharm, a Philadelphia, Pennsylvania-headquartered CDMO, reported last month (August 2020) that it had completed a facility expansion to its oral solid-dose manufacturing operations with the commissioning of a highly potent compound contract manufacturing suite for clinical trial materials and commercial products. Key service equipment and set-ups include: a large-scale roller compactor, milling room, bin blender, tablet press, and ingress and egress airlocks with enhanced personnel controls.
Adare Pharmaceuticals. In April (April 2020), Adare Pharmaceuticals, a clinical-stage pharmaceutical company and a provider of pharmaceutical technologies, and a CDMO, acquired Orbis Biosciences, a Lenexa, Kansas-based pharmaceutical technology company with particle-size engineering technology that is used to produce uniform particles in size ranges suitable for use in oral solid dosage forms as well as in injectable and otic dosage forms.
CoreRx. CoreRx, a Clearwater, Florida-based CDMO of solid, liquid and semi-solid dosage forms, reported in August (August 2020) that its new product development center is operational. The site 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 to the Clearwater workforce over time. The new 26,000-square-foot space expands the capacity of its oral and topical dosage-form development group by increasing drug-product volume through several formulation technologies, including blending, roller compaction, wet granulation, fluid-bed drying, spray drying, and extrusion spheronization.
Velesco Pharma. In February (February 2020), Velesco Pharma, a provider of early- and late-stage drug-development services, began operations at its new cGMP clinical manufacturing facility in Wixom, Michigan. This facility operates in coordination with Velesco Pharma’s existing Wixom site, which houses its pharmaceutical research and development laboratories that provide formulation development, analytical method development, and testing services. The new facility replaces and consolidates the company’s existing manufacturing site in Kalamazoo, Michigan. The facility triples the company’s cGMP clinical trial manufacturing capacity and features expanded processing suite space to manufacture a range of non-sterile dosage forms, including liquids, semi-solids, powders, capsules, and tablets, including the capability to handle high-potency compounds.
Upperton Pharma Solutions. Upperton Pharma Solutions, a Nottingham, UK-based CDMO that develops and produces oral and inhalation drug products for clinical trials, reported earlier this year (2020) that it had invested £500,000 ($625,000) to expand its tablet-manufacturing capabilities with the addition of tablet-processing equipment for wet granulation, roller compaction, tablet compression, hardness testing, dedusting, weight sorting and tablet coating. The investment was made in 2019 and is continuing in 2020.
1. K. Sedo and T. Kararli, “Global Report–2019 Global Drug Delivery & Formulation Report, Part 1,” Drug Development & Delivery, March 2020, https://drug-dev.com/global-report-2019-global-drug-delivery-formulation-report-part-1-a-global-review/.
|Table I: Oral Solid Dosage (Tablets, Capsules) Products Approved as New Molecular Entities by the US Food and Drug Administration’s Center for Drug Evaluation and Research in 2020 (as of October 30, 2020)|
|Company||Property name (active ingredient); application type;||Indication||Dosage Form: Route of Administration|
|AstraZeneca||Koselugo (selumetinib sulfate); NDA||Neurofibromatosis type 1, a genetic disorder of the nervous system causing tumors to grow on nerves||Capsule; Oral|
|Bayer Healthcare||Lampit (nifurtimox); NDA||Chagas disease in certain pediatric patients younger than age 18||Tablet; Oral|
|Biohaven Pharmaceuticals||Nurtec ODT (rimegepant sulfate); NDA||Migraines||Tablet, Orally Disintegrating; Oral|
|Blueprint Medicines||Gavreto (pralsetinib); NDA||Non-small-cell lung cancer||Capsule; Oral|
|Blueprint Medicines||Ayvakit (avapritinib); NDA||Adults with unresectable or metastatic gastrointestinal stromal tumors||Tablet; Oral|
|Bristol-Myers Squibb/Celgene||Zeposia (ozanimod hydrochloride); NDA||Relapsing forms of multiple sclerosis||Capsule; Oral|
|Deciphera Pharmaceuticals||Qinlock (ripretinib); NDA||Advanced gastrointestinal-stromal tumors||Tablet; Oral|
|Eli Lilly and Company/Loxo Oncology||Retevmo (selpercatinib); NDA||Lung and thyroid cancers||Capsule; Oral|
|Epizyme||Tazverik (tazemetostat hydrobromide); NDA||Epithelioid sarcoma||Tablet; Oral|
|Esperion Therapeutics||Nexletol (bempedoic acid); NDA||Adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C||Tablet; Oral|
|Incyte||Pemazyre (pemigatinib); NDA||Certain patients with cholangiocarcinoma, a rare form of cancer that forms in the bile ducts||Tablet; Oral|
|Neurocrine Biosciences||Ongentys (opicapone); NDA||Patients with Parkinson’s disease experiencing “off” episodes||Capsule; Oral|
|Novartis||Tabrecta (capmatinib hydrochloride); NDA||Non-small cell lung cancer||Tablet; Oral|
|Otsuka||Inqovi (cedazuridine; decitabine); NDA||Adult patients with myelodysplastic syndromes||Tablet; Oral|
|Recordati Rare Diseases||Isturisa (osilodrostat phosphate); NDA||Adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease||Tablet; Oral|
|Seagen (formerly Seattle Genetics)||Tukysa (tucatinib); NDA||Advanced unresectable or metastatic HER2-positive breast cancer||Tablet; Oral|
|ViiV Healthcare||Rukobia (fostemsavir tromethamine); NDA||HIV||Tablet, Extended Release; Oral|
NDA is new drug application.
Bristol-Myers Squibb acquired Celgene in November 2019.
Eli Lilly and Company acquired Loxo Oncology in February 2020.
Viiv Healthcare is a joint venture between GlaxoSmithKline, Pfizer and Shionogi.
Source: Center for Drug Evaluation and Research, US Food and Drug Administration.
|Table II: Non-Solid Dosage Products Approved as New Molecular Entities by the US Food and Drug Administration’s Center for Drug Evaluation and Research in 2020 (as of October 30, 2020)|
|Company||Property name (active ingredient); application type;||Indication||Dosage Form: Route of Administration|
|Acacia Pharma Group||Byfavo (remimazolam besylate); NDA||Sedation||Powder; Intravenous|
|Acacia Pharma Group||Barhemsys (amisulpride); NDA||Preventing nausea and vomiting after surgery||Solution; Intravenous|
|Amivas||Artesunate (artesunate); NDA||Severe malaria||Powder; Intravenous|
|Cassiopea||Winlevi (clascoterone); NDA||Acne||Cream; Topical|
|Dr. Reddy’s Laboratories||Xeglyze (abametapir); NDA||Head lice||Lotion; Topical|
|Eli Lilly and Company/Avid Radiopharmaceuticals||Tauvid (flortaucipir F-18); NDA||Diagnostic agent for patients with Alzheimer’s disease||Solution; Intravenous|
|Gilead Sciences||Veklury (remdesivir); NDA||COVID-19 in certain specified patients||Injectable; Injection|
|Gilead Sciences/Immunomedics||Trodelvy (sacituzumab govitecan-hziy); BLA||Adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease||Injectable; Injection|
|GlaxoSmithKline||Blenrep (belantamab mafodotin-blmf); BLA||Multiple myeloma||Injectable; Intravenous|
|Horizon Therapeutics Ireland||Tepezza (teprotumumab-trbw); BLA||Thyroid eye disease||Injectable; Injection|
|Jazz Pharmaceuticals||Zepzelca (lurbinectedin); NDA||Metastatic small-cell lung cancer||Powder; Intravenous|
|Lundbeck||Vyepti (eptinezumab-jjmr); BLA||Preventive treatment of migraine in adults||Injectable; Injection|
|MorphoSys||Monjuvi (tafasitamab-cxix); BLA||Relapsed or refractory diffuse large B-cell lymphoma||Injectable; Injection|
|Nippon Shinyaku||Viltepso (viltolarsen); NDA||Duchenne muscular dystrophy||Solution; Intravenous|
|Novo Nordisk||Sogroya (somapacitan-beco); BLA||Growth hormone||Solution; Subcutaneous|
|RadioMedix||Detectnet (copper dotatate CU-64); NDA||Detection of certain types of neuroendocrine tumors||Solution; Intravenous|
|Regeneron Pharmaceuticals||Inmazeb (atoltivimab; odesivimab; maftivimab); BLA||Ebola virus||Solution; Injection|
|Roche’s Genentech||Enspryng (satralizumab); BLA||Neuromyelitis optica spectrum disorder||Injectable; Injection|
|Roche’s Genentech||Evrysdi (risdiplam); NDA||Spinal muscular atrophy||Solution; Oral|
|Sanofi||Sarclisa (isatuximab-irfc); BLA||Multiple myeloma||Injectable; Injection|
|Sebela Pharmaceuticals||Pizensy (lactitol); NDA||Chronic idiopathic constipation in adults||Solution; Oral|
|Trevena||Olinvyk (oliceridine); NDA||Management of acute pain in certain adults||Injectable; Intravenous|
|Ultragenyx Pharmaceutical||Dojolvi (triheptanoin); NDA||Molecularly long-chain fatty acid oxidation disorders||Liquid; Oral|
|Viela Bio||Uplizna (inebilizumab-cdon); BLA||Neuromyelitis optica spectrum disorder||Injectable; Injection|
|Zionexa||Cerianna (fluoroestradiol F-18); NDA||Diagnostic imaging agent for certain patients with breast cancer||Solution; Intravenous|
BLA is biologics license application.
NDA is new drug application.
Avid Radiopharmaeutials is a subsidiary of Eli Lilly and Company.
Gilead Sciences acquired Immunomedics in October 2020.
Sebela Pharmaceuticals acquired Braintree Laboratories in 2018.
Source: Center for Drug Evaluation and Research, US Food and Drug Administration.