Consumables and contract manufacturing the drivers of the bioprocessing industry

Despite its consolidation, the competitive consumable sector still offers potential for rapid growth and better profits in the biopharmaceutical industry, while contract bioprocessing services will be increasingly in demand, according to a new market report by D&MD Publications titled "The Bioprocessing Industry - Increasing Capacity, Production, and Efficiency."

With approximately one-fourth of new drugs coming on the market being biopharmaceuticals and annual sales projected to surpass $52bn (€41bn) by 2010, there is a growing thirst for raw materials, equipment and contract production to support bioprocesses found in a manufacturing flow sheet, such as mass cell culture, centrifugal cell separation, filtration, several types of chromatographic separation and the creation of stable final formulations, probably including lyophilisation of the final product.

Most of this demand comes from the US, which now comprises more than 1,500 biotech companies with revenues just over $72bn, whereas Europe is lagging behind with 17 per cent of the global market and revenues approximating $12bn. The Asia/Pacific region has around 700 companies with revenues of $2bn but is catching up.

The drugs they make vary from antibiotics, hormones and enzymes to monoclonal antibodies, prophylactic agents and immune and cell response modifiers. These are produced using microbial or animal cell expression systems or in transgenic animals or plants.

One of the most significant markets in the bioprocessing industry is in the supply of culture media and their components. In this sector, the supply of animal blood serum-based media supplements, especially fetal bovine serum, is experiencing change as there has been a drive toward the use of serum-free media to improve safety and reduce processing.

This international business is split between two major players, Invitrogen and HyClone, and about four smaller suppliers, according to the report.

As far as capital equipment is concerned, which represents about 40 per cent of the cost of a new good manufacturing practice (GMP) facility, the market has seen significant condensation, in which multifirm companies are still acquiring more smaller companies and adding to their product range and geographical coverage.

Examples include the SP Industries conglomerate, which now contains both major US manufacturers of lyophilisers and Thermo Electron in the centrifuge market.

To a certain extent, this has reduced competition, although most operations still promote specific product ranges under their original brand names.

The world market for the pilot to production-scale bioreactors and fermentors is estimated at $380m, but it fluctuates widely, since capital expenditure on large custom plants can represent this figure from one installation, but this is not an annual event, the report says.

Since the technologies are also applicable to other industries, estimates of the value of the bioprocessing industry to the manufacturers of centrifuges, homogenisers, mills, and filter holders is difficult, but since one piece of major equipment may sell for $250,000 to $1m, and a custom plant may cost several millions of dollars, the bioprocessing "hardware" market must be of the order of $100m to 500m.

Nevertheless, manufacturers of large sterile disposable containers and accessories are promoting a trend away from the static tank/pipe type of installation.

On a scale of perhaps up to 500L per batch, this trend may already be having an effect and it is likely to continue to do so, the report predicts.

In the chromatographic separations sector, GE Healthcare leads the field, but there are at least fifteen other companies with appreciable market shares. Total sales are around $980m per annum, with separations, principally chromatography equipment and media, yielding approximately $400m of this.

This is possibly the most valuable bioprocessing sector, especially in terms of its consumables, but that position may be held by the filter business, the report suggests.

The bioprocessing microfiltration and ultrafiltration business is dominated by two large multinational companies, Millipore, which is now only servicing the biopharmaceutical and research industries, having spun off its microelectronics business as a separate company, and the biopharmaceutical segment of the Pall Corporation.

A third company, Sartorius of Germany, is gaining increased market share in certain specialist applications in the ultrafiltration segment.

In all, the biopharmaceutical industry spends at least $800m if not more each year on filters and filtration equipment.

In bioprocess analysis and control, high-performance liquid chromatography (HPLC) and electrophoretic gel separations are the most commonly used techniques.

Waters is now the world leader in HPLC systems and has extended into mass spectrometry. The company has sales of almost $860m, of which approximately 60 per cent is in HPLC sales alone.

Of particular promise is the late-stage development and GMP contract manufacturing segment, where the bioprocess industry chiefly operates. There are approximately 70 companies in the world currently offering contract manufacturing services. About 30 are based in or have operations in North America, the remainder are principally in Europe, with one company each in Japan, Singapore, South Korea, South Africa and Australia.

The worldwide contract manufacturing market for biopharmaceuticals was valued at approximately $1.3bn 2003 and by 2010 it is projected to exceed $3.7bn.

A 2004 survey indicated that approximately 35 per cent of biopharmaceutical companies outsourced some of their biomanufacturing activities, ranging from bioprocess development to commercial manufacturing. This number is expected to grow to 47 to 50 per cent by 2008.

Current projections, based upon the number of monoclonal antibody products currently in the clinical trial pipeline, point to a serious shortfall developing within three years in manufacturing capacity, especially in mammalian cell culture.

Several major contractors are in the process of expanding their capacity, but the determination of the future demand is fraught with uncertainty, the report warns.

There is concern in the management of contract manufacturers that, if their expansions are too late, they will be forcing clients to reconsider creating or expanding their own facilities so that the new capacity, when it is finally available, may be in excess of demand.

In fact, several manufacturers have already decided to go it alone, rather than rely upon the availability of contract capacity.

A shortage of experienced, GMP-trained staff to operate new capacity, whether in the sponsor companies or in the contractors, may exacerbate the problem.

The report ends by stressing that the bioprocessing industry will make a major contribution to the growth of recombinant therapeutic drugs and will reap a concomitant benefit from its efforts to develop and market new and better bioprocessing tools.