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    Features

    Oral Solids Endure & Evolve

    Contract service providers discuss the state of the oral solid dose development and manufacturing market.

    Oral Solids Endure & Evolve
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    By Tim Wright, Editor, Contract Pharma03.01.19
    The oral solid dose (OSD) development through manufacturing pipeline of products is expanding at a robust rate—even while industry watches the investment, interest and demand for biologics and biosimilars growing rapidly. There are several reasons OSDs continue to be the most popular dosage form for getting drugs to patients. In addition to being cost effective and relatively easy to make compared to their large molecule counterparts, they are most importantly, patient friendly, especially among the pediatric and geriatric populations.

    Another reason they remain popular is that OSDs hold substantial opportunity in extending product lifecycles, and thereby leveraging growth potential. Manufacturers of OSDs today are employing various life cycle management patent strategies, including the development of new drug formulations such as extended, controlled, or rapid release formulations.

    Future Market Insights (FMI), in a recent report, projected the global oral solid dosage pharmaceutical formulation market to register 6.5% CAGR during the forecast period 2017 to 2027. In terms of revenue, the market reached nearly $500 billion in 2017 and is expected to surpass the $900 billion mark by 2027.

    While oral solid products may seem a bit unfashionable compared with the steep increase in new biopharmaceutical products, they nevertheless will continue to constitute a major share of all medicines for the foreseeable future, according to Torkel Gren, senior director, science and technology officer, Recipharm AB. “Interestingly, there is also a lot of new product development in this area,” he said. “Many of these products in development are improved formulations of existing dosage forms, such as modified or controlled release, and can offer significant advantages.”

    Michael Reel, director of technical services at Alcami said the contract development and manufacturing organization (CDMO) sees a broad range of clients in the OSD manufacturing market. “On one end of the spectrum, there are companies with extensive knowledge and experience in drug development, looking for a partner that can provide capacity,” he said. “On the other end, there are emerging organizations seeking expertise in bringing their product through the various phases and to the market. Recognizing that these companies are an innovation engine for the industry, Alcami focuses on understanding and serving them to drive change and positively impact the industry through development and launch of new treatments.”

    North America Still Largest Piece of the Pie
    In the foreseeable future, North America will remain the largest market for oral solids, followed by Asia-Pacific Excluding Japan (APEJ) and Western Europe. Revenue from the market in North America is expected to surpass $300 billion by the end of 2027, according to the FMI report. In addition, APEJ is projected to reach revenue worth $295 billion by the same time.

    In terms of dosage form, tablets will continue to remain preferred in the market, with sales estimated to climb past the $500 billion mark by 2027. Sales of tablets are anticipated to exhibit the highest CAGR in the market, ftollowed by capsules, which are expected to register 6% growth.

    Based on release mechanism, immediate release will remain dominant in the market, expanding at 6.4% CAGR through 2027. Immediate release is expected to generate revenue over $400 billion by the end of 2027. Controlled release formulations are expected to register 7.4% growth during the same time period.

    The FMI report also noted that Latin America is emerging as an important manufacturing hub for oral solid dosage forms on the back of availability of low-cost resources. In fact, propelled by investments from multinational companies that are focusing on expanding their presence in this region, Latin America is expected to have the fastest growth pace in the market, expanding at 9.2% CAGR through 2027.

    In other growth markets, the emergence of affluent consumers in APEJ countries such as China, India and Korea are boosting growth of the oral solid dosage pharmaceutical formulation market in this region. Consumers here are adopting western lifestyles, leading them to suffer western lifestyle-related diseases including diabetes, cancer and obesity, which is contributing to market growth in APEJ. However, factors such as decreasing productivity of Asian manufacturers and containment issues, and low R&D expenditure coupled with challenges incurred in U.S. FDA compliance are expected to impede growth of the market in APEJ.

    OSD Growth Drivers
    Several factors are influencing the solid oral dose market, according to Justin Schroeder, senior executive director, global marketing and design, PCI Pharma Services. “Drugs are becoming increasingly targeted and specialized,” he said. “This leads to higher value medicines and creates more fragmented patient populations, impacting batch sizes and campaign volumes, in turn driving the need for increased efficiencies and more flexible equipment. At the same time, reduced scale manufacturing and packaging creates a more complex supply chain. This means that CDMOs need to look at alternative models to deliver efficiencies and remain competitive.”

    With the continued focus on quality and regulatory requirements, visible from the audit processes in which operators in today’s market are involved, supply chain assurance at every stage is driving changes in how companies operate, especially as globalization continues.

    “New markets are opening up,” Schroeder said, “providing significant opportunities for the pharmaceutical industry in terms of patient populations. The outsourcing industry therefore needs to evolve to support this growth. For companies utilizing services from the developing nations where differences in requirements may exist, careful management is needed to ensure global compliance.”

    Anil Kane, executive director, global head of technical and scientific affairs, Thermo Fisher Scientific, highlighted the rise in development of new chemical entities (NCEs) for cancer and immune therapy as a key driver in today’s market. “The number of NCEs being evaluated for various cancers and immunotherapies has been on the rise over the past 3 years and we see this trend continuing to gain interest,” he said. “Oral solid development continues to be of interest in this therapeutic area for reasons of convenience in dosing—in adult and geriatric segments of the population—as well as for compliance. This is also evident in the number of clinical trials being conducted on a global basis.”

    As the number of NCEs coming out of drug discovery are reducing, there is an enhanced focus on exploring line extensions and life cycle management strategies. “Approved drugs with established safety profiles as well as known pharmacokinetic profiles including tolerable doses are being explored for newer indications,” said Kane. “Clinical studies in humans can be expedited since safety and tolerability of the drug is no longer an issue. Understanding the new targets and mechanism of action, followed by establishing pharmacodynamic and clinical efficacy of a new disease state or indication is a new way to bring drugs faster to the patient and to the market.”

    In addition, delivering a combination of drugs is another strategy being used. “Combining two or more established drugs is not a new life cycle management strategy, however, fixed dose combinations for a new indication offers another opportunity to use the established safety profiles of drugs and evaluate new doses for an entirely new indication,” said Kane. “We see many new organizations and start-ups exploring these opportunities to bring combination drugs to market and to patients.”

    Opportunities & Challenges
    While there is a growing interest for more specialized products often with relatively low production volumes, at the same time there is also a continued interest in new products with improved properties based on old drug substances. “Globally, there is a lot of manufacturing capacity for solid dosage forms,” said Recipharm’s Gren. “Unfortunately, a lot of this capacity was designed to suit the old ‘blockbuster’ paradigm. Today, the demand is for more flexible solid manufacturing capacity. Non-standard dosage forms, smaller batches and difficult active pharmaceutical ingredients (APIs) are examples of areas that are increasingly important. The challenge lies in being able to adapt current operations to offer more flexible manufacturing operations.”

    According to Alcami’s Reel, today’s OSD formulations are becoming more complex. “Compounds with low solubility and/or high potency demand innovative formulas to achieve the desired results,” he said. “Sustained release and controlled release formulations remain increasingly popular. Throughout the manufacturing process, sources of potential extractables and leachables must be identified.”

    There has also been a lot of focus on ensuring high and reproducible oral bioavailability of poorly soluble drug substances and, as a result, several technologies are now available to cater for these products, added Gren. “Coated pellet technology has been around for a long time, but now we are seeing a strong interest in this technology as it is useful for modified release and fixed dose combinations, as well as products that combine both these concepts,” he said. “Mini-tablets have also been around for a while but demand is growing as they are well suited to many combination products and allow for flexible dosing.”

    With many of today’s NCEs being highly potent compounds, according to Thermo Fisher’s Kane, the nature of these drugs in clinical manufacturing requires handling under containment to prevent exposure to personnel. “Processing and packaging of these high potent compounds is challenging but can be done safely using contained equipment,” he said. “Thermo Fisher has invested in the build out of engineering controls and equipment to support handling high potent compounds.”

    With the focus on oncology specifically, PCI is also supporting the development, manufacturing and packaging of many more highly potent compounds. “This is an area where we have made significant investments in both world-class technology as well as expert and experienced staff, supporting processes for total containment of drug product,” he said. “This expertise and specialization allows us to provide our clients with a seamless development-to-commercialization, or ‘molecule-to-market’, pathway with drug development, clinical and commercial scale manufacturing, clinical supply packaging and logistics, commercial launch and ongoing supply for the entirety of the drug lifecycle.”

    Moving forward, a major driver for business success is flexibility, according to Reel. “While plans are made and schedules defined before the project begins, knowledge gained as the project progresses requires adjustments to the schedule,” he said. “One of the most challenging aspects is maintaining the agility and flexibility to react to changing protocols. The ability to communicate effectively and to make adjustments rapidly and smoothly is key to bringing projects to fruition.Client requirements in early phase studies often evolve based on clinical results. This frequently means redevelopment or expansion of the dosage range covered by manufacturing. Being able to respond to changes that benefit the patient is critical to our success as a CDMO.”

    In the end, Schroeder said the outsourcing and partnership segment is flourishing. “Vendor consolidation leads to growth, in turn leading to additional investment,” he said. “As long as we continue to listen to our customers to understand exactly what they need, and invest in the best solutions, we are looking forward to continued and sustained growth.” 
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