ABSTRACT
This paper compares two project alternatives for the construction of a new 100 kg antibody plant, based on a real case. The
chosen hybrid approach, which integrates disposable and stainless steel technologies, is compared with an equivalent stainless-steel
model, in terms of capital investment, operating costs, and net present value.
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Disposable technology has gained importance in recent years. One of its significant advantages is that it reduces the initial
capital burden and spreads out capital costs more evenly over the life of a manufacturing project.1 A fully disposable plant is still a technological dream, however. That concept has some potential applications in small-scale
production, or in pilot plants for process development, but seems less likely to have a significant impact on the current
paradigm for large-scale biotech plants that have fermentation capacity greater than 100,000 L.2
There is less doubt nowadays, however, that a combination of disposable and reusable equipment is beneficial for process economics
in both new and existing manufacturing plants. Such hybrid models can be applied with different degrees of disposable integration,
and that degree generally depends mainly on process scale and the biotech manufacturers' experience with disposable technology.
Mid-size plants will probably benefit the most from the use of this hybrid model, but data from real case studies are not
yet available to validate this hypothesis.
The Center of Molecular Immunology (CIM), in Havana, Cuba, has built a strong pipeline of new antibodies and cancer vaccines.
Some of these products are in early research, and others are in clinical development or commercial distribution. Several years
ago, to meet this growing demand to produce therapeutic grade antibodies, CIM began the design and construction of a new plant
with an annual capacity of 100 kg.
CIM has integrated disposable technologies into its biopharmaceutical processes for more than 10 years, and the use of disposable
technology has been a key element in CIM's approach to process innovation, cost control, and regulatory robustness. Current
applications include plastic culture ware and disposable systems for formulation operations and medium handling up to 2,500
L. Based on this practical experience, a new antibody active pharmaceutical ingredient (API) production plant was designed
to integrate disposable technology to the extent that it has been validated in our processes. This approach was chosen to
maximize our antibody production capacity in a context of limited capital availability.
In contrast to most large facility investment projects carried out by biotech companies, CIM's manufacturing project is based
on continuous perfusion culture rather than the more widespread fed-batch fermentation. Because of the higher productivity
of perfusion, production levels similar to those of the fed-batch mode can be achieved with smaller fermentation volumes.
However, the high medium turnover required for the continuous operation of perfusion requires the use of several medium and
harvest storage vessels for each production fermenter. A large-scale perfusion operation also involves almost daily purification
runs (usually hundreds of lots per year) with intensive buffer preparation and storage operations. In our case, all this led
to a smaller, but more sophisticated, manufacturing facility compared to a typical biotech plant.
This paper discusses the economic comparison of two project alternatives for the construction of a new 100 kg antibody plant,
based on a real case. The antibody plant, with its significant integration of disposable technology, will be referred to as
the "hybrid project" (HYB) and will be compared with an equivalent stainless-steel (SS) project based on reusable equipment.
The two project alternatives will be compared in terms of capital investment, operating costs, and net present value.
