By Tim Wright, Editor, Contract Pharma03.01.18
Oral solids continue to be the most common dosage form in the pharmaceutical market. They are cost-effective, easy to manufacture and patient-friendly. 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, according to Justin Schroeder, executive director, marketing, business development and design, PCI Pharma Services, in terms of “relatively uncomplicated packaging needs and storage and distribution requirements due to chemical and physical stability.”
Future Market Insights forecasts the global oral solid dosage pharmaceutical formulation market to grow from $493.2 billion in 2017 to $926.3 billion by 2027, representing a compound annual growth rate (CAGR) of 6.5%. According to IMS Health, nine of the top 10 drugs based on monthly prescription volume are oral solid doses and the top selling drug by sales figures is also an oral solid dose.
“Growth in the oral solid dose outsourcing market remains strong despite the fact that competition continues to increase,” said Kimberly McClintock, executive vice president, Metrics Contract Services. She pointed out that external funding from venture capital sources has been very active, driving an increase in the number of early-phase development programs.
Key Trends
Although the market has seen the growth of biologics and small-molecules often delivered parenterally or via alternative routes, solid dosage products continue to dominate the existing pharmaceutical landscape while enjoying a healthy share of new product development. “However, while the growth of biologics in the marketplace is likely to hamper the growth of the oral solid dosage formulation market over time, the solid dose outsourcing market remains strong,” said Mr. Schroeder.
Anil Kane, executive director, global head of technical and scientific affairs, Patheon, said he is seeing an increasing number of life cycle management strategies being executed. “Controlled release formulations to reduce the frequency of dosing and thereby improve patient compliance are on the rise,” he said. “Pediatric products continue to grow as well due to changes in regulatory requirements in this area and the opportunity of obtaining an exclusivity period.”
Also discussing pediatric products, Mr. Schroeder said the adoption and 2012 reauthorization of the Best Pharmaceuticals for Children Act (BPCA) provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity, as well as the Pediatric Research Equity Act (PREA), which requires drug companies to study their products in children under certain circumstances.
“While some of these pediatric medicines are developed as traditional oral solid dose, drug companies may opt for powder delivery forms for the numerous benefits in delivery to this population,” he said. “With the proper formulation, these powder therapies can be utilized by parents by virtue of being mixed with water or juice as an oral suspension, or potentially mixed with palatable foods such as yogurt or apple sauce. Therefore, the market may experience an increase in powder for reconstitution development in an attempt to address this need.”
In addition, fixed dose combinations (FDCs) offer a popular line extension opportunity to potentially achieve synergistic clinical effects of multiple active pharmaceutical ingredients (APIs) in a pill while reducing the pill burden on patients.
Mr. Kane also said the market is seeing off patent drugs being evaluated for potential benefits in completely new indications. “Shelved molecules are resurfacing,” he said. “New chemical entities that were evaluated in preclinical toxicology and found safe but did not meet early candidate selection criteria due to priority reasons and were shelved, are now being re-evaluated.”
A key trend, according to Ms. McClintock, is the use of co-processed and multi-functional excipients, which scientists can utilize to speed up the formulation development process for oral solid dosage products. She also said the commercial manufacture of smaller batch sizes is affecting both pharmaceutical companies and contract service providers.
“Oncology medications are not your traditional large production volume products and never will be,” she said. “This poses a challenge to both sides: How does the pharmaceutical company find a commercial manufacturer suitably structured to economically deliver a low-volume product, and how does the commercial manufacturing organization price such work to remain profitable? Both sides must work together to find a solution that benefits the parties involved.”
At PCI, Mr. Schroeder said the company has seen a shift in development projects toward more complex potent molecules, driven primarily by oncological products. “Manufacturing of solid dosage forms itself requires a range of processing technologies, and a real understanding of the product and how it behaves during processing,” he said. “The more specific the action, the more potent the molecule. The more potent the molecule, the more complex the therapy, and the more complex the therapy, the more complex the processing requirements.
“Further still, the more complex the processing requirements, the more complex the formulation optimization. The Quality by Design (QbD) approach to development has led to a better understanding of the variables that influence product development and this is of particular importance when processing highly potent molecules. This has led to a real need within the marketplace for contract development and manufacturing organizations (CDMOs) being able to offer a more specialist service for the development and manufacturing of such molecules.”
Growth Opportunities
While there continues to be a need for expanding capabilities for specialized dosage forms such as modified-release, pediatric-geriatric, and abuse-deterrent formulations, another growth opportunity for CDMOs, according to Ms. McClintock, is to expand integrated offerings by adding services such as clinical packaging and distribution. “Continuous processing is also becoming a more widely accepted practice, especially with large pharma and biotech clients. However, this also can prove to be a challenge for a CDMO since it requires large upfront costs, making it difficult to pull the trigger for investment.”
Mr. Schroeder reiterated that the opportunities for growth in solid dose formulations lie in the potent arena, primarily driven by oncological products, but also in other treatment areas including those used for pain relief and for treatments relating to the central nervous system (CNS).
“With over 200 cancers identified, the market shows no sign of slowing in terms of the pace of development, especially for some of the more rare cancer types whereby FDA fast track to designated orphan/ultra-orphan status is possible,” he said. “By the same token, the market growth in biologics and non-solid dose formulations is also increasing and as a result, CDMOs will need to diversify to meet this demand.”
For Patheon’s Mr. Kane, it’s the new phase of digital health and digitized drug products and technologies based on digitization and electronic tagging that will be of interest in the next several years and could revolutionize the industry.
“There is a lot of literature to show that drugs are not effective because patients do not adhere to the prescribing instructions. They do not take the right dose at the right frequency of administration,” he said. “Ingestible sensors in drug products that can monitor drug intake along with measurement of biometrics that sends this data to a physician or service provider through a wireless network promises to improve patient adherence and ultimately healthcare. The individual sensors have a unique identification code of the product, lot number, manufacturing details; and this data will also ensure the right medication is taken by the patient and will avoid counterfeit drug products in the market.
“These technology-enabled approaches give pharmaceutical companies the power to scan a pill found anywhere in the world and immediately confirm its authenticity, place and date of manufacture, lot number, and other product intelligence directly from the dosage form itself, without ever needing the product packaging,” he said. “According to a CNN report, between 100,000 and one million people die each year from counterfeit drugs. Contract developers and commercial manufacturers could have a big role to play in advancing these technologies for clinical or commercial drug products by partnering with technology developers and sponsor companies.”
Customer Expectations
Customer expectations for aggressive early-phase timelines continue to grow as the U.S. Food and Drug Administration (FDA) has granted more than 400 orphan designations annually within the past several years, according to Ms. McClintock. “Customer expectations for high-quality scientific expertise and value-priced services remain steady,” she said. “At the same time, they also expect a higher degree of flexibility from CDMOs. In the development space, clients are looking for a collaborative relationship with their CDMOs. This is not a new or evolving trend, but one that becomes more demanding each year. CDMOs must determine the right balance between utilization of resources in collaboration activities, versus delivery of milestones expected by clients. Investments made in project management and support functions will help, but CDMOs still often face difficult decisions to keep clients happy.”
Another key driver, she said, is the ability of CDMOs to meet the increased demands of shorter timelines. “Clients, their investors, and their patients all want to see new products entering clinical trials and, subsequently, the market more quickly,” she said. “While this demand remains constant, CDMOs must continue to maintain a high level of quality standards within a regulated industry. This driver has CDMOs evaluating internal systems, processes and procedures to become as efficient as possible to help clients meet their milestones.”
Customer expectations are very high and it is important to remember that often the molecules in question are very expensive and in short supply, and therefore development programs are required that maximize outputs while minimizing wastage, according to Mr. Schroeder. “Traditional early stage development can prove troublesome due to the time and cost involved in the formulation and analytical development, and so new and novel technologies should be assessed,” he said.
One such technology available would be Xcelodose micro-dosing, a system providing drug in capsule (DIC) capabilities. “At the early stages of development, such a system reduces the time and cost involved in traditional development by putting API directly into capsules and in turn, delivering drugs into patients earlier within the cycle,” said Mr. Schroeder. “This approach can reduce time, costs, and wastage and provide a faster ‘yes’ decision in terms of further development and equally the ‘fail and fail fast’ should a molecule show no therapeutic benefit. Again, the identification of a CDMO able to offer diversity in their approach to early stage development could be of interest to a pharmaceutical company.”
Other benefits exist, according to Justin Schroeder, executive director, marketing, business development and design, PCI Pharma Services, in terms of “relatively uncomplicated packaging needs and storage and distribution requirements due to chemical and physical stability.”
Future Market Insights forecasts the global oral solid dosage pharmaceutical formulation market to grow from $493.2 billion in 2017 to $926.3 billion by 2027, representing a compound annual growth rate (CAGR) of 6.5%. According to IMS Health, nine of the top 10 drugs based on monthly prescription volume are oral solid doses and the top selling drug by sales figures is also an oral solid dose.
“Growth in the oral solid dose outsourcing market remains strong despite the fact that competition continues to increase,” said Kimberly McClintock, executive vice president, Metrics Contract Services. She pointed out that external funding from venture capital sources has been very active, driving an increase in the number of early-phase development programs.
Key Trends
Although the market has seen the growth of biologics and small-molecules often delivered parenterally or via alternative routes, solid dosage products continue to dominate the existing pharmaceutical landscape while enjoying a healthy share of new product development. “However, while the growth of biologics in the marketplace is likely to hamper the growth of the oral solid dosage formulation market over time, the solid dose outsourcing market remains strong,” said Mr. Schroeder.
Anil Kane, executive director, global head of technical and scientific affairs, Patheon, said he is seeing an increasing number of life cycle management strategies being executed. “Controlled release formulations to reduce the frequency of dosing and thereby improve patient compliance are on the rise,” he said. “Pediatric products continue to grow as well due to changes in regulatory requirements in this area and the opportunity of obtaining an exclusivity period.”
Also discussing pediatric products, Mr. Schroeder said the adoption and 2012 reauthorization of the Best Pharmaceuticals for Children Act (BPCA) provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity, as well as the Pediatric Research Equity Act (PREA), which requires drug companies to study their products in children under certain circumstances.
“While some of these pediatric medicines are developed as traditional oral solid dose, drug companies may opt for powder delivery forms for the numerous benefits in delivery to this population,” he said. “With the proper formulation, these powder therapies can be utilized by parents by virtue of being mixed with water or juice as an oral suspension, or potentially mixed with palatable foods such as yogurt or apple sauce. Therefore, the market may experience an increase in powder for reconstitution development in an attempt to address this need.”
In addition, fixed dose combinations (FDCs) offer a popular line extension opportunity to potentially achieve synergistic clinical effects of multiple active pharmaceutical ingredients (APIs) in a pill while reducing the pill burden on patients.
Mr. Kane also said the market is seeing off patent drugs being evaluated for potential benefits in completely new indications. “Shelved molecules are resurfacing,” he said. “New chemical entities that were evaluated in preclinical toxicology and found safe but did not meet early candidate selection criteria due to priority reasons and were shelved, are now being re-evaluated.”
A key trend, according to Ms. McClintock, is the use of co-processed and multi-functional excipients, which scientists can utilize to speed up the formulation development process for oral solid dosage products. She also said the commercial manufacture of smaller batch sizes is affecting both pharmaceutical companies and contract service providers.
“Oncology medications are not your traditional large production volume products and never will be,” she said. “This poses a challenge to both sides: How does the pharmaceutical company find a commercial manufacturer suitably structured to economically deliver a low-volume product, and how does the commercial manufacturing organization price such work to remain profitable? Both sides must work together to find a solution that benefits the parties involved.”
At PCI, Mr. Schroeder said the company has seen a shift in development projects toward more complex potent molecules, driven primarily by oncological products. “Manufacturing of solid dosage forms itself requires a range of processing technologies, and a real understanding of the product and how it behaves during processing,” he said. “The more specific the action, the more potent the molecule. The more potent the molecule, the more complex the therapy, and the more complex the therapy, the more complex the processing requirements.
“Further still, the more complex the processing requirements, the more complex the formulation optimization. The Quality by Design (QbD) approach to development has led to a better understanding of the variables that influence product development and this is of particular importance when processing highly potent molecules. This has led to a real need within the marketplace for contract development and manufacturing organizations (CDMOs) being able to offer a more specialist service for the development and manufacturing of such molecules.”
Growth Opportunities
While there continues to be a need for expanding capabilities for specialized dosage forms such as modified-release, pediatric-geriatric, and abuse-deterrent formulations, another growth opportunity for CDMOs, according to Ms. McClintock, is to expand integrated offerings by adding services such as clinical packaging and distribution. “Continuous processing is also becoming a more widely accepted practice, especially with large pharma and biotech clients. However, this also can prove to be a challenge for a CDMO since it requires large upfront costs, making it difficult to pull the trigger for investment.”
Mr. Schroeder reiterated that the opportunities for growth in solid dose formulations lie in the potent arena, primarily driven by oncological products, but also in other treatment areas including those used for pain relief and for treatments relating to the central nervous system (CNS).
“With over 200 cancers identified, the market shows no sign of slowing in terms of the pace of development, especially for some of the more rare cancer types whereby FDA fast track to designated orphan/ultra-orphan status is possible,” he said. “By the same token, the market growth in biologics and non-solid dose formulations is also increasing and as a result, CDMOs will need to diversify to meet this demand.”
For Patheon’s Mr. Kane, it’s the new phase of digital health and digitized drug products and technologies based on digitization and electronic tagging that will be of interest in the next several years and could revolutionize the industry.
“There is a lot of literature to show that drugs are not effective because patients do not adhere to the prescribing instructions. They do not take the right dose at the right frequency of administration,” he said. “Ingestible sensors in drug products that can monitor drug intake along with measurement of biometrics that sends this data to a physician or service provider through a wireless network promises to improve patient adherence and ultimately healthcare. The individual sensors have a unique identification code of the product, lot number, manufacturing details; and this data will also ensure the right medication is taken by the patient and will avoid counterfeit drug products in the market.
“These technology-enabled approaches give pharmaceutical companies the power to scan a pill found anywhere in the world and immediately confirm its authenticity, place and date of manufacture, lot number, and other product intelligence directly from the dosage form itself, without ever needing the product packaging,” he said. “According to a CNN report, between 100,000 and one million people die each year from counterfeit drugs. Contract developers and commercial manufacturers could have a big role to play in advancing these technologies for clinical or commercial drug products by partnering with technology developers and sponsor companies.”
Customer Expectations
Customer expectations for aggressive early-phase timelines continue to grow as the U.S. Food and Drug Administration (FDA) has granted more than 400 orphan designations annually within the past several years, according to Ms. McClintock. “Customer expectations for high-quality scientific expertise and value-priced services remain steady,” she said. “At the same time, they also expect a higher degree of flexibility from CDMOs. In the development space, clients are looking for a collaborative relationship with their CDMOs. This is not a new or evolving trend, but one that becomes more demanding each year. CDMOs must determine the right balance between utilization of resources in collaboration activities, versus delivery of milestones expected by clients. Investments made in project management and support functions will help, but CDMOs still often face difficult decisions to keep clients happy.”
Another key driver, she said, is the ability of CDMOs to meet the increased demands of shorter timelines. “Clients, their investors, and their patients all want to see new products entering clinical trials and, subsequently, the market more quickly,” she said. “While this demand remains constant, CDMOs must continue to maintain a high level of quality standards within a regulated industry. This driver has CDMOs evaluating internal systems, processes and procedures to become as efficient as possible to help clients meet their milestones.”
Customer expectations are very high and it is important to remember that often the molecules in question are very expensive and in short supply, and therefore development programs are required that maximize outputs while minimizing wastage, according to Mr. Schroeder. “Traditional early stage development can prove troublesome due to the time and cost involved in the formulation and analytical development, and so new and novel technologies should be assessed,” he said.
One such technology available would be Xcelodose micro-dosing, a system providing drug in capsule (DIC) capabilities. “At the early stages of development, such a system reduces the time and cost involved in traditional development by putting API directly into capsules and in turn, delivering drugs into patients earlier within the cycle,” said Mr. Schroeder. “This approach can reduce time, costs, and wastage and provide a faster ‘yes’ decision in terms of further development and equally the ‘fail and fail fast’ should a molecule show no therapeutic benefit. Again, the identification of a CDMO able to offer diversity in their approach to early stage development could be of interest to a pharmaceutical company.”
