New divisions of players
Industry therefore faces a pressing conundrum: how to manage the quality and compliance of pharmaceutical manufacturing, which
has lagged behind other industries even in the best of times, during a period of cost-cutting and fragmentation, with a myriad
of manufacturers of various degrees of sophistication in a variety of countries and cultures. At the same time, our country
seeks to increase manufacturing as a percentage of the US economy as a means of remaining competitive as a nation. We propose
here that these two imperatives are related and can be managed in an integrated fashion.
It is useful to separate pharmaceutical manufacturing, both primary and secondary, into two groups: those operations that
have become conventional and essentially commoditized, which are now being executed around the globe, and which are unlikely
to return to the US; and those operations which relate to novel, "smart" products and processes that are knowledge-intensive,
have IP protections, and are less sensitive to labor costs.
In the case of the first group, commoditized manufacturing, quality and regulatory compliance remain crucial. Indeed, quality
compliance has become more challenging in the outsourced-manufacturing environment because it now must be managed across many
more intercompany barriers. Fortunately, a solution has been demonstrated in the chemical industry. The answer is to make
manufacturing technology mature, transparent, and portable. The operations involved must be categorized and described in detail,
making it possible to harmonize methods, approaches, operations, control algorithms, and quality tests, such that the operations
can be understood fundamentally, modeled mathematically, and then executed under predictive-model controls as is done by other
high-tech industries. This approach addresses quality concerns while also raising the technological and scientific expectation
for producers, making it more likely that manufacturing can once again be performed in the US.
The later group of "smart" products and processes involve targeted drugs and delivery systems, personalized medicine, medicines
prepared locally on demand, complex hybrid biologics, sensors, and new diagnostics. These technologies are enormously promising,
but they require long-term fundamental research to create new products, new manufacturing methods, and new technologies to
achieve goals like rapid, high-precision microdosing, self-assembled targeted delivery nanoparticles, and so forth. The players
in this area are a diverse set of companies and universities from around the world that typically work in a disconnected fashion,
perhaps entering into complex, bilateral (and sometimes asymmetrical) agreements.
In such an environment, it is hard to assess which approaches and products have the most merit, and how they could function
together in different and synergistic combinations. The best options may take a long time to come to market or may not be
created at all. These are the products that we must ensure get developed and manufactured in the US.
A plan forward
Given this environment, re-energizing pharmaceutical manufacturing in the US is likely to take place only if a coherent plan
is implemented. In the authors' opinion, such a plan must address four crucial elements: strong long-term technology development,
a nurturing ecosystem where collaborations among innovation players are facilitated while transactional costs between them
are minimized, science-based compliance with high quality standards, and a concerted effort to create and maintain a highly
skilled labor pool capable of supplying the needs of industry, government, and academia. Thus, we propose a strategy involving
the following components:
1. Create a long-term, strategically driven research center, bringing industry, academia, and government together. The center
would be devoted to developing the advanced technologies that will give birth to the next generation of products (patient-specific
therapies, point-of-need manufacturing, drug-sensor combination products, in-situ diagnostics). Such a center could play a similar role as the Sematech consortium (
http://Sematech.org/) played for the microelectronics industry since the mid-1980s, which led to a broad revival of US-based research and manufacturing
in a critical industry.
2. Develop a well-funded, agile innovation ecosystem where technology customers (i.e., finished goods commercialization companies)
and technology suppliers (e.g., NME suppliers, equipment and instrumentation companies, CROs, CMOs, commercial integrators,
and universities) can work together effectively, with access to funding, and with minimal transactional overhead. By treating
process development and manufacturing technology as precompetitive activities, members who never interact or interact only
pairwise in transactional arrangements, would then interact as a group and through partnerships rather than through transactions.
A set of standards, approaches, and controls for the commoditized processes and products can be created in this environment,
with ongoing consultation with regulatory agencies so that the standards can become part of regulatory expectations.
3. Establish a regulatory science center that can provide scientific support to the FDA and to ensure that regulations are
updated, transparent, and promote higher quality standards while decreasing regulatory risk. This center would create a system
to communicate and share development and manufacturing issues with the industry so that they are not repeated numerous times,
and will create a repository of the most basic and necessary science that must be applied, as a minimum, to all process and
4. Enable training and educational programs that ensure a supply of properly skilled labor for all of the noted parties. To
rejuvenate pharmaceutical product and process development and manufacturing in the US, an entire generation of pharmaceutical
(and their management) must be educated, or in some cases, re-educated on modern product and process engineering methodologies.
This approach is entirely feasible. One of the few silver linings of the recent massive restructuring in US-based branded
pharma is that there is a ready supply of available scientists eagerly awaiting the opportunity to upgrade their technical
skills. It is hard to conceive a better use of educational resources than to devote them to this purpose.
A plan such as the one proposed here will not happen spontaneously. It will take time and effort. It will take leadership
and aggressive advocacy. However, if we consider the alternative, which is to let yet another great American industry leave
our shores, the path forward appears self-evident.
To advance these goals, the authors plan to organize a Summit Meeting at Rutgers University in Spring 2012 to gather input
from all sectors and to develop concrete plans. We call all leaders in the pharmaceutical industry, government, and academia
to join us in an effort to bring these ideas to Washington.
Fernando Muzzio, PhD, is director of NSF Engineering Research Center at Rutgers University and a member of the PharmTech editorial advisory board.
Mauricio Futran, PhD, is professor and chair of the Department of Chemical and Biochemical Engineering at Rutgers University, email@example.com