LONDON -- The U.K. BioIndustry Association (BIA) is calling on the government to formulate a national plan for the development of a biopharmaceutical manufacturing base, following an investigation into the state of biotechnology manufacturing.

The BIA points to "profound ignorance" of the role that manufacturing will have to play if drug candidates are to be successfully commercialized.

Paul Edwards, who chaired the investigation by the BIA's manufacturing advisory committee, said there has long been concern over how the industry manages the transition from being largely discovery-based to being a fully integrated industry sector. "This transition will require the industry to cope with the need to produce materials to meet the requirements at all stages of development, from the clinical trials phase right through to product commercialization." But, as yet, there is little appreciation of the fact that the processes involved in biopharmaceutical manufacturing are significantly more complex than, and often in no way comparable to, those involved in the manufacture of small-molecule chemical entities, the report said.

The industry needs to build up biotechnology manufacturing at a time when the U.K.'s traditional pharmaceutical manufacturing base is losing out to countries with lower costs and more favorable tax and grant arrangements. In the past three years, 17 large U.K.-based pharmaceutical companies have cut back on manufacturing in the U.K., while in the same time, 11 of these have announced significant investments outside the U.K. This has led to a 15 percent cut in jobs in this part of the pharmaceutical sector.

The committee's report, "Making the Manufacturing Breakthrough," said all companies, including start-ups, should plan for production of sufficient quantities of drug material for initial preclinical and clinical studies. At the same time, the inexorable compression of the drug-development cycle means that manufacturing must be considered from the early stages of development. "Companies ill-informed of this reality face the prospect of serious delays to their drug programs, delays which may be exacerbated by finite cash availability," the report said.

Employment Patterns To Shift

Even companies that intend to license out drugs after the early stages of development face growing regulatory pressure to produce drugs for clinical trials with the same rigor as the eventual manufacturing process. Few facilities for producing materials to this standard for clinical trials are located in the U.K.

As a result, there is a need for an educational program to alert companies to the intricacies and technical challenges of manufacturing. There is also a need to carry out a skills audit, and -- as an integral part of a national strategy -- to ensure that university courses are set up to provide the required skills.

The maturing of the biotechnology sector will lead to a shift in employment patterns towards manufacturing. Such a shift has occurred in the U.S., where in 1990, 72 percent of those employed in the industry were involved in research and development, with none in manufacturing. By 1998, 55 percent were busy in research and development, and manufacturing accounted for 19 percent of bioindustry employment. The report notes that while the output of graduate biologists in the U.K. is 5,000 per year, the output of graduate biochemical engineers in only 50 per year. (The U.S. produces 750 biochemical engineers annually.)

Computer-Based Processes Urged

Process technology pioneered in other sectors must be transferred to biopharmaceutical manufacturing, the report said. This includes the use of computer-based process models; systematic approaches to evaluating process options; and rapid monitoring for capturing analytical information in real time. "The medicines of the human genome era are likely to be targeted at smaller sub-groups in the population and manufacturing will need to follow this trend with new approaches to mass customization of the kind that are being applied to sectors such as consumer electronics and the automobile industry," said the report.

In August 1998, the U.K. government launched a two-year program to encourage the development of a strong manufacturing base in biotechnology. The program aims to ensure that companies can move seamlessly from the research-and-development phase through commercialization.

At the launch of the program, Industry Minister John Battle said it was possible that companies which have invested heavily in developing compounds will falter when it comes to manufacturing them. "Current low levels of awareness could leave companies vulnerable in a number of fast-moving areas such as regulatory compliance, cost containment and new manufacturing techniques," he said. The program includes training grants; the setting up of information networks to provide specialists' technical advice; help for small companies to assess contract manufacturers; and the promotion of research in bioprocessing.

Biopharmaceuticals account for 5 percent of world pharmaceuticals by market value. However, by number they make up 13 percent of the new therapeutic entities in development, with around 500 currently in clinical trials. *