The Impact of AdCEV/egg Vectors at the Manufacturing Process Level
Eggs account for approximately 50% of bulk vaccine cost in inactived influenza vaccine manufacturing.7 Recombinant vectors offer a way of lowering vaccine cost by reducing the number of eggs required for a given yield. For
example, a 10-fold increase in yield could result in a 40% reduction in vaccine cost. In addition, by producing more vaccine
per unit operating time, inactived influenza vaccine production can be accelerated. Even a 3- to 5-fold reduction in the number
of eggs required would dramatically improve manufacturing logistics and have the follow-on effect of enhancing quality control.
Smaller, Less Complex Facilities
Simplifying production can improve quality. In recent years, the complexity of large-volume vaccine manufacturing has led
to quality problems and FDA regulatory actions among even the most experienced manufacturers.8 The AdCEV/egg system facilitates production by allowing a common approach to facility design, wherein multiple vaccines
can be made with process differences mostly confined to downstream steps.
The higher expression yields achieved through molecular-level improvements would enable a reduction in facility size and complexity,
dramatically reducing the costs of design, construction, licensure and operation.
Higher yields result in smaller processing volumes (<1,000 L), which work well with new single-use manufacturing technologies.
For example, process streams could be easily conveyed between processing stages in single-use containers, eliminating the
need for complex transfer lines and piping systems. Such a facility might typically use a modest 8,000 ft2 of ISO 7 and 8 classified space, with a similar amount of space for utilities, enabling manufacturers to enhance the quality
of vaccines and better comply with GMP requirements.
An Improved Technology Transfer Platform
A scaleable, integrated manufacturing concept called the Poultry Pharm is being developed as a deployment model for AdCEV/egg-based manufacturing. A turn-key Poultry Pharm consists of a fertilized
egg production facility (or supply source) operationally linked to an incubation and bioprocessing suite where recombinant
proteins can be manufactured using AdCEV and other egg-based vector technologies. Lean design and construction makes it possible
for Poultry Pharms to be quickly and inexpensively deployed with a reduced timeline for design, construction, and commissioning—in
months rather than years (Figure 2). We achieved a dramatic reduction in projected facility cost estimates from $45 to 85
million to <$15 million at full validation (Table 2) using modern modular manufacturing approaches.
Figure 2. Rapid 12-month timeline for the design and construction of a modular GMP vaccine facility.
Furthermore, the Poultry Pharm franchise concept enables a bottom-up approach to technology transfer for vaccine production,
building on existing agro-industrial and human capacity in the developing world, while providing support to ensure international
standards of quality control for locally produced products. Future developments of such manufacturing platforms will require
(i) the development of disease surveillance that can integrate with product development cycles, (ii) the evolution of design
specifications for manufacturing facilities using the AdCEV/egg platform and single-use equipment, and (iii) review of modern
manufacturing facility design and operation approaches with regulatory agencies such as the FDA, EMEA, and WHO to gain support
Table 2. Cost centers and actual budget for the design and construction of an 8,000 ft2 GMP vaccine facility.