Pharmaceutical manufacturers are feeling the heat. With cost containment a priority, especially in an era of COVID-19 and the threat of other previously unimagined business disruptions, the race to outsource development and manufacturing of life-saving drugs to trusted service providers is accelerating.

The race for end-to-end outsourcing with contract manufacturing organizations (CMO) and contract development and manufacturing organizations (CDMO) takes on different meanings for smaller and virtual manufacturers compared with large conventional pharmaceutical companies. With fewer financial and human resources, smaller organizations rely on their outsourcing partners for additional services that many large manufacturers retain internally. Although smaller firms have equal dependence as large drug companies on their CMO/CDMO partners, their priority is focused on a different set of service offerings.

Origins of Outsourcing
Manufacturing is no longer a profit center for drug companies. When the economics of the situation became apparent during the mid-1990s, financial companies and venture capital (VC) firms swooped in. Their plan involved purchasing unprofitable business units from manufacturers and running them on their behalf. During these early years, the strategy did not unfold smoothly. The VC firms underestimated the reluctance of manufacturers to forfeit control over their manufacturing operations. More recently, skepticism was replaced with willingness as companies sold manufacturing and development operations that negatively affected the bottom line.

Outsourcing Drivers
The current drive from pharmaceutical manufacturers for outsourcing activities along a wider stretch of the supply chain is due to several factors. 

First, there is a growing demand for generic medicines and biologics. The U.S. Food and Drug Administration (FDA) approved 1,171 generic drugs during their fiscal year 2019, a higher quantity compared with all previous years. During the same period, the FDA approved 48 new drugs and biologics. 

Second, the development and manufacturing of medications is a capital-intensive business. With margins shrinking for generics, manufacturers are reducing the scale of their investments within this category.
Third, complex manufacturing methods and equipment are required for new molecular structures and for the increasing sophistication of active pharmaceutical ingredient (API) materials.

Manufacturers conserve resources by relying on outsourcing partners to expand their role leading to product commercialization. Consolidation of development and manufacturing activities with CMO/CDMO partners reduces cost, conserves resources, enables the manufacturer to focus on drug substance development and adds flexibility with access to equipment options beyond internal capabilities. 

One-stop Shopping
The CMO/CDMO market is competitive and resistant to consolidation with only a few large players with global reach. The ability to differentiate services is an important factor for increased business. Promoting multiple outsourced services as a one-stop-shop for manufacturers is a popular strategy.  

Different CMO/CDMO companies pursue this profitable goal in one of two ways. The first pathway is a vertically integrated model built around API and excipient manufacturing. The second strategy is a virtually outsourced model that centers on performing quality and regulatory services with an acquired API source.

Vertically-outsourced Model
Pharmaceutical manufacturers that utilize a vertically outsourced model partner with CMO/CDMO firms that create their own API, excipients and components and often maintain project management responsibilities internally.

This one-stop-shop model applies to larger organizations partnering with large manufacturer clients with branded products and international marketing reach. 

Many of the clients retain personnel internally specializing in regulatory, quality assurance and commercialization. Due to their size, these clients have subject-matter experts on staff to actively communicate with the CMO/CDMO and manage the project from start to finish.

Benefits of the vertically outsourced solution include consistency of product quality in all commercial markets globally because in many cases, one company is manufacturing the API for 100% of production. 

Virtually-outsourced Model
Unlike vertical outsourcing, middle to small-market clients utilizing the virtually outsourced solution work with their CMO/CDMO partners to source API and all components. Virtual manufacturers and smaller manufacturers with limited financial and human resources partner with these firms. 

Many virtual manufacturers are substantial business entities so revenue alone is not a defining quality of companies seeking the virtual outsourced model. However, many companies pursuing this route are smaller with limited resources. Regardless of the size of their bottom line, these clients also tend to rely on their outsourcing partner for project management responsibilities that are internal functions within most larger manufacturers.

Another distinguishing characteristic for clients of CMO/CDMO companies specializing in a virtual one-stop shop model is their preference for projects with regional or national scope. Vertically outsourced firms are better equipped for commercialization on a global scale.

Manufacturers working with virtually outsourced CMO/CDMO partners do not have the resources or expertise to develop their own API. In this scenario, the CMO/CDMO partner manages procurement of API from trusted sources and creates alliances with companies providing complementary services including Third Party Logistics (3PL) capabilities and serialization support for DSCSA compliance.

Although large CMO/CDMO companies may perform non-core activities for clients, these tasks are generally completed with more efficiency by a smaller scale CMO/CDMO that engages in these functions on a daily basis for multiple clients.

End-to-end Relationships
The differences between vertical and virtual outsourcing are quantitative in terms of services provided and also qualitative regarding the relationships between parties. 

Many manufacturers partnering with vertically outsourced CMO/CDMO companies have operations in multiple countries and employ internal teams with deep expertise in compliance, quality assurance, development, manufacturing and materials management to oversee activities of their CMO/CDMO partner. These interactions tend to be knowledge-neutral in the sense that both the client and CMO/CDMO have similar levels of expertise.

Relationships in the virtually outsourced model tend to be weighted toward the CMO/CDMO partner in cases where a small virtual manufacturer engages a contract manufacturer to manage the entire commercialization process. In some instances, the CMO/CDMO serves as a general consultant performing non-core functions including preparation of documents for the client to submit to authorities, customs and brokerage services and third party logistics solutions.

Examples of Virtual Outsourcing
A typical example of virtual outsourcing involves a small virtual manufacturer that partnered with a virtually outsourced CMO/CDMO to produce a generic version of a branded medication. 

The CMO took ownership of the challenge and identified the regulatory stages required to support their submission to the FDA for approval. Documentation was created and prepared by the CMO on behalf of the client. These documents were submitted by the client for approval. A supply agreement was completed enabling purchase of API. Throughout the process, the project manager at the CMO communicated regularly with the client to review status and progress. When the API was acquired, the CMO arranged for importation and customs clearance to the manufacturing facility. 

With the API in hand, the CMO conducted analytical testing based on previously created scientific methods, followed by validation of all methods and materials.

For the manufacturing process to begin, all related components and excipients were researched, acquired and tested for suitability. A coordinated effort was organized to comply with DSCSA regulations for product serialization. This client also relied on their CMO to design the product label. As a final step, the client utilized a trusted partner of the CMO for third party logistics services.

In a second typical case, a smaller virtual manufacturer with comprehensive knowledge of pharmaceutical science that possessed less knowledge about commercialization approached a virtually-outsourced CMO/CDMO for assistance bringing their product to market. Their medication was approved in Canada and they were seeking FDA approval. The CMO/CDMO undertook the research and development required to submit proper documentation. This project included complete formulation development, analytical testing, method and material validation. Results and documentation were generated and prepared for submission by the client. In this case, the CMO/CDMO also referred the client to potential partners with sales and marketing expertise in anticipation of entry into the U.S. market. 

Virtually outsourced CMO/CDMO companies attempt to broaden their knowledge base as much as possible because the skillset of their client base varies considerably. The virtually outsourced CMO/CDMO must be prepared for research and development projects as well as procurement of critical components—bottles, pumps, sprayers, droppers—to meet project requirements for safety, efficacy and cost. And sometimes project requirements change unexpectedly as when a client requests a custom-designed label that was not envisioned before contract signing.

Conclusion
The goal of innovative CMO/CDMO partners to offer ‘end-to-end’ solutions takes on different meanings depending on the desired client base. Larger-scale CMO/CDMO companies begin their end-to-end services with development and manufacture of the API and progress through each service with regular oversight by the client company. This vertically-outsourced business model focuses on large manufacturers with a global presence. These manufacturers maintain internal departments with specific knowledge of regulatory compliance, quality assurance, pharmaceutical development, sales and marketing that work alongside their CMO/CDMO partners.

Contrast the vertically-outsourced model with the virtually-outsourced model for providing end-to-end services. CMO/CDMO companies offering virtually-outsourced solutions cater to virtual or smaller manufacturers with limited geographic reach. These CMO/CDMO partners acquire API from trusted sources and tend to oversee project management on behalf of their clients. Relationships in the virtually-outsourced model focus on guiding the client through the development and commercialization process. In many cases these clients do not have the resources to maintain subject-matter experts and therefore rely heavily on their CMO/CDMO partner for recommendations and insights to reach the finish line.

Future Prospects
Vertical and virtual end-to-end outsourcing models are poised for further growth. As the coronavirus pandemic compels new strategies to better prepare for future disruption, the pharmaceutical outsourcing industry will benefit from increased reliance on domestic development and production of medications to enhance security and guarantee supply. 

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Scott Cohon is the Director of Sales and Trade Relations at Woodfield Pharmaceutical, LLC.  He is responsible for expanding relationships with current clients and trading partners. In his role Scott evaluates changing needs of manufacturers and implements services that support commercialization strategies.