Consider the manufacturing streams for biologics expressed in E. coli: plasmid construction, cell transformation, fermentation, protein recovery, refolding, purification, analytical evaluation,
validation, engineering, and regulatory compliance (Figure 1). Each of these areas requires specific expertise and professional
skill sets, although not necessarily equally nor concurrently. How does a company manage this quandary, retaining both professionals
and supporting infrastructure?
Figure 1. Throughout the manufacturing steps (plasmid construction through regulatory compliance) involved in manufacturing
a biologic expressed in E. Coli, specific expertise is required at a number of varying stages during the manufacturing strategy.
The skills sets such as molecular biologist, process engineer, and regulatory manager are needed for shorter, definite intervals,
whereas the collective skill sets (shown in ovals) are required on a more lengthy basis, possibly even throughout the entire
duration of the manufacturing program (depending on the program).
By outsourcing, an organization can gain access to an entire complement of skill sets like these, as well as to new generation
or proprietary technologies, all the while reducing overall developmental risk. Outsourcing offers flexibility, allowing the
organization to refocus asset utilization on its own core competencies, saving time, money, and potential heartache.
FACTORS IN OUTSOURCING PROCESS DEVELOPMENT
At Hospira, we have identified important factors that organizations contemplate when determining whether their operations
will benefit from outsourcing process development.
Economic Efficiency and Opportunity Cost
Resource mismanagement and production inefficiency can have long-term, detrimental effects on investor confidence. Maximum
economic efficiency is key to a healthy ROI.
Economic efficiency embodies both allocative and production efficiency. Allocative efficiency is the allocation of resources
to the products most desired, and production efficiency is the adoption of least costly production techniques. Operating outside
the realms of maximum efficiencies, and thus comparative advantage, is damaging and unsustainable. Opportunity cost is therefore
an important consideration when deciding whether to outsource.
Reduction in COGS
Compared with the manufacture of small molecules, the manufacture of biologics is eminently labor intensive, very technical,
more costly, and inefficient.6 At Hospira, we have determined two key elements that drive the COGS for biologics: molecular complexity and quantity required.
Protein length and sequence affect yield and purification efficiency whereas quantity requirements affect the scale of production.
Each factor ultimately determines the choice of production systems, e.g., chemical synthesis or recombinant manufacture, or
bacterial or mammalian-based expression systems. Production processes will also inevitably evolve as developmental requirements
A company needs to decide if it is capable of supporting the necessary production systems, taking into consideration compliance
issues. Process development contractors are using innovative, state-of-the art manufacturing technologies to expand production
capabilities and efficiencies. As such, the industry is seeing an array of new proprietary technologies, particularly those
having significant effects on production yields and protein purities. Amateur production is no longer realistic.