STANDARDIZING FACILITIES AND PROCESSES
Adapting manufacturing capacity to shifting demands in the market is like piloting a supertanker; one must anticipate changes
in direction and initiate responses well in advance. Manufacturing facilities take up to five years to build and validate,
and up to $800 million in capital investment. Thus, there is little ability to respond quickly to unpredictable markets that
sometimes change on a weekly basis.
A case in point can be found in recombinant factor VIII, developed in the 1990s for the treatment of hemophilia A. Three companies,
Baxter International, Bayer, and Wyeth had each developed a competing product, and initially could not meet growing demands.
New manufacturing facilities were built to meet this demand. However, by the time the facilities came online, their total
capacity exceeded the market needs and the companies had to manage overcapacity. For Wyeth, that meant making the tough decision
of selling one of its plants to another biotechnology company in need of capacity. It has been said that over 50% of existing
plants are manufacturing different products than those that were initially intended for them.
The ability of companies to predict and anticipate clinical as well as market demands throughout discovery, development, and
commercialization remains elusive. Most drugs today are targeted to so-called "blockbuster" markets consisting of large patient
populations. Larger manufacturing facilities require several years' lead time to come online, and during that time a successful
clinical outcome is not ensured. In fact, with less than one in five drug candidates surviving clinical trials to reach the
market, investing in manufacturing facilities before regulatory approval becomes a strategic gamble. Even drugs predicted
to be "blockbusters" could end up serving niche markets if results from pivotal clinical trials lead to indication restrictions.
The industry has adapted to these conditions by making frequent use of contract manufacturing or in some cases by establishing
partnerships with competing companies to share capacity to offset the risk of idle plants (due to overcapacity) or lost sales
(due to insufficient capacity). Such a partnership was formed between Wyeth and Genentech in 2005 when Wyeth was contracted
by Genentech to produce an antibody against the HER2 protein (used in the treatment of breast cancer). This arrangement allowed
the companies to react quickly to surges in product demand and offset the cost and risk of idle manufacturing plants.
The economic solutions of contract manufacturing and capacity-sharing are only possible because of extensive standardization
that has taken place in the industry. Standardizing manufacturing technology and equipment has emerged as the result of two
major factors: (1) a limited number of engineering companies that have experience in designing biotechnology facilities have
been building similar facilities for each customer, and (2) a limited number of high-capacity contract manufacturing facilities
have implemented a similar technology base in order to serve clients with a wide variety of products. While standardization
has enabled a more flexible response to markets through capacity sharing, many manufacturing processes still have low yields
resulting in products that are expensive to produce.
PLATFORM TECHNOLOGY IMPLEMENTATION
In addition to biology and process technologies, improvements in manufacturing efficiency have been achieved through workflow
improvements and platform implementation. The implementation of a consistent platform technology has been driven by the fact
that the large majority of biotechnology products are antibodies. In a sense, most products have similar requirements in process
development, and optimizations can be more easily translated from one product to the next. At Wyeth, the development of a
pipeline candidate may be approached in a fairly standard fashion: production cell line candidates are identified using a
high-throughput technology; the final choice of production cell line is based on performance in the "platform process" using
standardized culture medium, culture conditions, and duration, with certain variations. Similarly, the downstream purification
process uses a platform approach. The purification conditions for each molecule can be identified using high-throughput methodology
resulting in high product yields and purity from a two-column process. Raw materials, production equipment, quality procedures,
fermentation technology and methods as well as batch monitoring and documentation, are generally kept consistent. This is
especially important when a product is manufactured at multiple locations, facilitating technology and knowledge transfer
between sites. It is also an advantage for rapidly switching and optimizing products at a single facility.