The trend towards outsourcing solid dose manufacturing has been driven by the ever more complex nature of new molecules. Innovators are choosing to share the burden of challenges relating to bioavailability, formulation, stability, manufacturability and, not to mention, scalability. Industry pressures to reduce development times and costs, as well as increasing numbers of smaller drug developers now taking molecules to market independently, are spurring partnerships with contract development and manufacturing organizations (CDMOs) who can bring formulation expertise, global experience and broad service offerings. This article looks at the growing market for oral solid dose (OSD) development, addressing the operational challenges faced. It will also shed light on how outsourcing may be key in bringing increased flexibility and capacity to the manufacture of these drug forms.

The solid dosage landscape
It was expected among industry peers that OSD manufacturing activity would decline when, in fact, the opposite has been true. There are many reasons why OSD forms remain the most popular, including their relative ease of manufacture, cost-effectiveness and patient-friendly nature. They also offer significant benefits to manufacturers such as trouble-free packaging and transportation, as well as increased chemical and physical stability.¹ In addition, they present an opportunity to extend product lifecycles. Advances in drug delivery are now enabling OSDs to achieve better bioavailability through the adoption of novel drug delivery technologies, such as extended, controlled and rapid release systems. From the patient perspective, these can offer inherent advantages in dose administration and can be formulated in varying dosage forms to increase patient compliance.

Future Market Insights (FMI) forecasts the global OSD pharmaceutical formulation market to grow from $493 billion in 2017 to $926 billion by the end of 2027. This represents a value compound annual growth rate (CAGR) of 6.5% over the forecast period.¹

As demand has shifted from a ‘blockbuster’ paradigm to more complex active pharmaceutical ingredients (APIs) and smaller batches, OSD development and manufacturing poses operational challenges for pharmaceutical firms. Today, many changes are occurring in OSD manufacturing with different chemistries being used that require new approaches and the implementation of continuous processing. Demand is therefore high for CDMOs that can bring both formulation expertise in this area, as well as flexible manufacturing capacity.

Solid dose projects
Today, the industry is seeing evidence that three types of manufacturing projects are driving the OSD outsourcing market. First, there are customers with high volume products that are looking for an improved set-up from a total cost of supply point of view. While previously customers would typically consider just the cost of contract manufacturing, they are increasingly recognizing that there are other factors at play. For example, the location of manufacturing can cause issues, slowing down the supply chain and, in some cases, jeopardize supply.

With more products requiring complex manufacturing processes, developers are also struggling to find the required technical set-up which is also manageable from a cost standpoint. Consequently, they are recognizing that CDMOs that can offer a breadth of capabilities may be better positioned to help them simplify their supply chain during OSD manufacturing projects.

Finally, it is becoming more and more common that relatively small/virtual companies are developing new drugs that they do not intend to manufacture themselves. In this case, they are choosing to partner with CDMOs with development capabilities from the start.

Outsourcing advantages
Outsourcing not only serves to streamline development processes, while offering more flexible manufacturing, but it can bring wider access to expertise, helping to mitigate risk for developers. It also reduces the need for in-house resources and allows a developer’s team to focus on core R&D competencies.

Despite OSD drugs being one of the oldest, most popular forms, their development and manufacture still presents many challenges and opportunities. The need for specialized processing technologies to enable controlled release products, satisfy containment needs and produce combination products with several APIs, is one of the main drivers for increased outsourcing. Responsive and flexible CDMOs that possess the ability to address the challenges and leverage the opportunities can help alleviate much of the perceived burden for developers.

In selecting a CDMO, customers should look for a clean compliance record, good supply service and a strong reputation for on-time delivery, as well as value for money through an attractive total cost of supply. Increasingly, developers expect that a CDMO will take responsibility for project management. Consequently, being able to forge a strong, strategic relationship and build solid communication with a partner is becoming a more fundamental part of the outsourcing partnership; improving efficiencies and reducing costs cannot be achieved without dialogue and understanding between developer and supplier. Therefore, close attention should be paid to how a CDMO intends to set-up a pragmatic communication network between themselves and the developer.

It is also critical to consider early on if a CDMO’s capabilities are compatible with a developer’s later stage requirements. This will be fundamental to achieving a seamless transition through the development phases into commercialization. Many developers prefer to work with CDMOs that can scale formulations from the laboratory to GMP clinical and ultimately commercial manufacturing. CDMOs that offer these capabilities can help to eliminate the risk, time and cost associated with technology transfer and the need to manage multiple suppliers. The robustness of manufacturing processes, capacity, trouble-shooting expertise and access to global resources are also key attributes that should be considered a priority for developers.

Another key driver should be the CDMO’s capability to meet shorter timelines while maintaining a high level of quality. Therefore, developers should look to gain a good understanding of the internal systems, processes and procedures that a CDMO has in place to be as efficient as possible in ensuring a project meets its milestones.

Developers should also seek to work with CDMOs that can offer a comprehensive understanding of their drug substance. A partner should understand how the substance behaves during processing, including its solubility in solvents and buffer systems, compatibility with excipients, stability under various physiological conditions, solid-state characteristics and physiochemical properties. These details will be essential in the selection of the right delivery system and the development of an optimal drug formulation. This point is particularly crucial in today’s industry where many challenging and complex compounds are subject to poor solubility. Finding the correct formulation solutions which are faster to scale-up and less likely to fail at a later stage of development is critical in a product reaching the point of commercial manufacture. 

In dealing with complex projects there will always be technical challenges. High volume projects also bring their own unique set of obstacles. Identifying a CDMO that can demonstrate expertise in navigating difficult manufacturing projects and can readily identify where any problematic areas are likely to exist is paramount to success.

Conclusion
While OSD products may seem outdated 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. At a time when more complex molecules are calling for more diverse technical requirements and supply chain needs, the outsourcing relationship has never been more important. 

CDMOs that can offer developers expertise in formulation development and can achieve seamless scale-up and technology transfer for commercial manufacturing offer a clear advantage in supporting the manufacture of complex OSDs. 

References

1. https://www.futuremarketinsights.com/reports/oral-solid-dosage-pharmaceutical-formulation-market

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Erik Haeffler is the vice president of manufacturing services and the head of sustainability at Recipharm. He is responsible for the group’s sustainability work, as well as its focus on operational and commercial excellence. As part of his role, Erik is continuously developing a model for working with multi-site projects and is accountable for operations development across the company, including elements such as project management resources, corporate IS and project/product sourcing decisions.