Biomanufacturing Capacity Quandary

There could be a serious glut of commercial scale mammalian cell culture capacity over the next five years. Then again, there could be a significant shortage. It all depends on how things develop in expression technology, the new product pipeline, and corporate strategies.

Jim Miller

Those divergent scenarios are contained in a new report from BioProcess Technology Consultants (BPTC, Acton, MA) "Mammalian Cell Culture Supply and Demand." (PharmSource is working with BPTC to publish the report.) The BPTC team, led by Howard Levine and Tom Ransohoff, has built a comprehensive model of the cell culture market in which they assess the impact of the major factors that will drive the demand for mammalian cell culture capacity during the 2008–2013 period (Figure 1). Those key factors include potentially blockbuster products in the biopharmaceutical pipeline and the realization of improved expression titers in commercial production.

BPTC's base case projections indicate that the biopharmaceutical industry is looking at an overall surplus of mammalian cell culture capacity over the next five years. However, that industry overview masks different dynamics in the captive and contract segments of the supply base. The BPTC report suggests that the major biopharmaceutical companies with substantial mammalian cell culture capacity of their own (companies like Amgen, Genentech, and Wyeth) are likely to operate at less than 70% capacity, despite having some of the largest product requirements.

Contract mammalian cell culture manufacturers, on the other hand, are forecast to be operating at nearly 80% capacity. For all practical purposes, that is close to full use because most manufacturers seek to maintain a capacity buffer to handle demand surges and other unexpected events. The tight contract supply situation is accentuated by the fact that there are only three contract manufacturers with the capacity to handle large commercial products—Lonza (Basel, Switzerland), Boehringer Ingelheim (Biberach, Germany), and Celltrion (Inchon, South Korea).

Figure 1

WILD CARDS

"Despite the forecast tight contract capacity, I would advise any CMO (contract manufacturing organization) evaluating a major investment in new mammalian cell culture capacity to look carefully at all of the factors which could influence the future capacity landscape," says BPTC's Ransohoff. That's because the range of outcomes for several key drivers of the forecast is quite wide.

Probably the biggest factor is the rate at which improved process yields are translated from the laboratory to the commercial production environment. Cell culture titers are improving rapidly, says Ransohoff, with 10 g/L already demonstrated in a few cases (compared to typical titers of 1–2 g/L for current commercial products). "One very significant question is how quickly these technological advances will be translated into plant floor productivity gains," says Ransohoff. He agrees with several recent analyses that indicate that wide adoption of the improved processes could lead to substantial overcapacity in the industry, but he cautions that not all of the currently marketed products nor late stage pipeline products will achieve those kinds of yields over the next five years.

Another big wild card in the outlook is the rate of new product approval and market uptake. Ransohoff notes that the pipeline contains at least nine products with the potential to require one ton of product within the first five years of launch. A downward shift in actual approval rates or market acceptance would result in even greater overcapacity, but better-than-expected approvals and market uptake could lead to even tighter capacity conditions.

ASSET SWAPS

Aside from the variability of the demand outlook, another reason to be cautious in building new contract mammalian cell culture capacity is the possibility that captive capacity could move into the contract market if significant overcapacity persists there. Major biopharmaceutical companies generally prefer not to be in the contract manufacturing business, but they will sell excess capacity from time to time to cover the high fixed costs of running a GMP-compliant biomanufacturing operation. For instance, Human Genome Sciences recently entered into agreements with Eden Biodesign and Diosynth to market and sell its excess capacity, and Novartis's Sandoz division has been active in the contract biomanufacturing business for many years.

Another possibility is that one or more major biopharmaceutical companies could sell underused mammalian cell culture production assets to a contract manufacturer. For instance, in 2006, Genentech sold its facility in Porriño, Spain, to Lonza, and in 2007, Lilly sold to CMC Biologics the biomanufacturing facility in Bothell, WA, that it acquired when it bought Icos. Further, should Genentech not exercise its option on the facility being built by Lonza in Singapore, this would keep another 80,000 L on the contract market.

BUYER BEWARE

The BPTC analysis suggests that biopharmaceutical companies intending to use contract manufacturers for their monoclonal antibodies or other products produced through mammalian cell culture need to monitor the contract manufacturing market carefully. The market's supply–demand balance could change quickly, so companies could find themselves going from a buyer's market to a seller's market in short order. Companies developing biopharmaceuticals are well advised to get to know the market as soon as possible, and to begin building relationships with potential manufacturing partners so they have capacity lined up when they need to make a manufacturing commitment.

Jim Miller is president of PharmSource Information Services, Inc., Springfield, VA, 703.383.4903, jim.miller@pharmsource.com