Issue Date: February 12, 2007
For Better Or Worse
IMPRESSIONIST LANDSCAPES, everyone knows, are misleading. Close to the canvas, points of color can look vivid and intense. But only by standing back do these paintings' collective messages come through. There's something to be gained from both the big picture and the up-close view. Add additional perspectives to your view, be they political, societal, or economic, and the pointillist package seems to portray more. The custom chemical industry, which consists of hundreds of separate companies making intermediates and active ingredients for pharmaceuticals, is like a pointillist painting. It takes more than one perspective to grasp what it's all about.
"Every company can have an interpretation of opportunities, can look at its project pipeline, and can paint a good story around it," says Nick Hyde, business director of Dowpharma. "But if you look at the custom manufacturing industry in total, there are enough signs that the overall climate justifies concern." This is especially true, he points out, for companies that don't have particularly unique technology or production capabilities. Although more cautious than other views expressed these days, Hyde's conclusion is well-considered.
Pharmaceutical companies are under pressure, and the industry's sales growth has slowed to about 5% per year. Hyde sees no clear signs of rising R&D productivity or more new products. Management changes, site closures, and job cuts are further evidence of tough conditions. "The situation in the pharmaceutical market and for the contract manufacturers who supply it remains unstable," Hyde says.
Companies that are cutting their own costs no doubt want cost cutting from their suppliers as well. "Pharmaceutical companies are probably taking for granted the low prices that their supply base has been suffering from for three or four years," Hyde says. "Suppliers also have been doing clinical manufacturing on a marginal cost basis, and I suspect pharmaceutical companies have gotten used to that too." For custom manufacturers, this unprofitable scenario "doesn't sound like a sustainable model," Hyde notes. "It makes me think we're heading for a continued period of instability."
The dearth of new pharmaceuticals that need manufacturing, despite some in-licensing and acquisitions by drug firms, has translated into several years of low capacity utilization for the custom chemical industry. The result is low productivity from assets, high competition for new business, and depressed profits, Hyde explains. "Last year, industry commentators continued to say that the average contract manufacturer was making a return below the cost of capital," he says. "In other words, the industry in the West on average is not reinvestment grade, so assets are gradually being 'consumed' and not replaced longer term."
Guy Villax, chief executive officer of the Portuguese pharmaceutical chemicals company Hovione, sees related dangers, especially for businesses that operate under Good Manufacturing Practices (GMP) regulations. "It's very likely that companies that have had tough financial times won't have invested, and by not investing for five years or so, they are likely to be out of GMP compliance," he says. "So capacity, even though it may be there, is not going to be considered by customers because it's not compliant."
An obvious threat for suppliers overall is that business will go elsewhere. China has surfaced as the low-cost source for basic intermediates, and India is becoming a reputable supplier of advanced intermediates and active pharmaceutical ingredients (APIs), which are the medicinal compounds in a drug formulation that includes inert fillers and other ingredients. According to data from the market research firm Frost & Sullivan, India has more than 70 GMP-compliant manufacturing plants, making it second only to the U.S.
Several of the operators of these plants have begun to look outward. In late 2005 and early 2006, a wave of Indian companies acquired custom chemical operations in the West (C&EN, Feb. 13, 2006, page 17). Meanwhile, diversified European companies have been repositioning their businesses after failing to receive the returns they expected from them. Some simply sold operations for much less than the substantial amounts they paid in the boom years of the late 1990s.
Where some see losses, others see opportunities. Nicholas Piramal India Ltd. (NPIL) acquired the British firm Avecia Pharmaceuticals in late 2005 and has aspirations to make its NPIL Pharma business one of the top three global players in custom chemicals. Last August it expanded capacity in Grangemouth, Scotland, for high-potency and cytotoxic substances. Shortly thereafter it launched NPIL Innovations, a unit dedicated to technology development in biocatalysis, chemocatalysis, and flow processing.
NPIL Pharma took another major step toward becoming a global player with its June 2006 purchase of Pfizer's Morpeth, England, site. The deal included a potential $350 million, five-year agreement with Pfizer to supply APIs. NPIL Pharma's contract manufacturing revenues now exceed $200 million per year, according to Executive Director Michael Fernandes. The company plans to make further investments in high-potency, technical, formulation, and scale-up capabilities in 2007.
Meanwhile, in August 2006, India's Dishman Pharmaceuticals & Chemicals paid $74.5 million for Solutia's pharmaceutical services business, consisting of the Swiss operation CarboGen Amcis. Solutia, now in the midst of bankruptcy reorganization, acquired the business in 2000 and has had it on the block at various times over the past two years. Specializing in high-potency substances, such as cytotoxic oncology drugs, CarboGen Amcis had sales in 2005 of about $65 million, a figure that doubled the size of Dishman's pharmaceutical chemicals unit.
IT MAY SEEM counterintuitive for Indian companies to acquire Western assets that they can't run any more cheaply than the previous owners and that likely could be replicated at home for less money. What they actually are buying is "access to blue-chip clients and to some of the largest markets for fine chemicals," industry consultant Jan Ramakers says. "Having manufacturing and marketing in the West is certainly one of the drivers, and they want to be seen as serious global players, respecting intellectual property in light of stricter patent legislation in India."
But even more important than assets, Ramakers says, is "the knowledge of the people who run the businesses and their networking and contacts." Acquirers, like NPIL and Dishman, want to buy into that expertise and those relationships, because even the most outstanding manufacturing assets aren't worth anything alone. Several industry insiders positioned to make deals tell C&EN they'd never acquire an idle plant. Instead, they say, the custom manufacturing business is "all about the people."
A case in point is India's Shasun Chemicals & Drugs, which purchased Rhodia's U.K.-based pharmaceutical chemicals business in April 2006. Shasun's Pharma Solutions unit reports that it has retained more than 98% of its customers while succeeding in integrating the U.K. operations with low-cost raw materials from India. With 12 commercial products and 14 drug molecules in Phase II and III development, Shasun Pharma Solutions expects sales of about $75 million in 2007 and forecasts annual sales growth of around 15%.
Beyond India, the trend toward mergers, acquisitions, and spin-offs continued through 2006 and into early 2007. Since its launch in late 2004, for example, Sigma-Aldrich's SAFC fine chemicals group has been finding pieces to add to its now nearly $500 million-per-year business. Among its more recent purchases, in mid-2006, were solid-state chemistry specialist Pharmorphix and Honeywell's facility in Ireland; the latter's sale marked Honeywell's exit from the API business.
The separation of custom manufacturing operations from large, diversified companies is often viewed as a good thing because of their different business dynamics. Managers of small and midsized companies focused on the fine chemicals market believe the businesses are better positioned to prosper in the hands of new owners. Among the new companies in this mold are Aesica Pharmaceuticals, Archimica, Corden PharmaChem, Excelsyn, Dottikon Exclusive Synthesis, KemFine, and Minakem.
Private investors have catalyzed the creation of many of these companies. In carving operations out of large corporations and making them independent, these investors have created businesses with increased flexibility and freedom for conducting transactions that will facilitate further consolidation.
"We've found interesting opportunities," says Achim Riemann, managing director of International Chemical Investors Group (ICIG), about the acquisitions his company has made. "And we have a couple of others in the pipeline." ICIG acquired the former Rutgers fine chemicals businesses, now called Weylchem, in 2005, and then Albemarle's French fine chemicals business in 2006. In October, ICIG bought Cambrex facilities in Ireland and Belgium and named them Corden PharmaChem. "We're following a platform strategy and want to build something in both the GMP and non-GMP areas," Riemann says.
ICIG doesn't make acquisitions based on any predetermined design, Riemann maintains. "It's just a matter of the attractiveness of the business and in some respects how it fits into what we already have." What makes an acquisition attractive is its price, he remarks, and the possibility for cost cutting, product portfolio optimization, new products, and synergies with other group companies.
"To be successful in this business, you need a certain critical mass, because the portfolio turnover has increased in recent years and there's less stability," Riemann explains. "You lose products to Chinese and Indian competition, and either you find additional new ones, or you have to restructure and scale down your operations. That's easier to manage if you have a broader portfolio, because then you have more options."
Other recent deals in the fine chemicals arena include those by Aptuit, a drug development firm founded in late 2004 with the backing of private equity investors. In 2006, it expanded in the API area by acquiring EaglePicher Pharmaceutical Services and the solid-state chemistry specialist SSCI.
JUST LAST MONTH, Rockwood Holdings sold Novasep, which has annual sales of about $370 million, to a group of Novasep managers and outside investors. And the French chemicals group SNPE is considering strategic options for its $260 million fine chemicals business, the bulk of which is known as Isochem.
Archimica debuted in 2006, when Clariant sold its pharmaceutical fine chemicals business to the private equity firm TowerBrook Capital Partners. The Germany-based business has sales in excess of $250 million, much of it from the former BTP, a company Clariant acquired for $1.8 billion in 2000. With businesses in specialized building blocks and starting materials, GMP intermediates, and APIs, the business includes essentially all the related assets and personnel that were previously part of Clariant.
Archimica managers believe that being a focused and stable "pure play" business will allow the firm to be more responsive to customer needs. "We believe that the pharmaceutical culture is fundamentally different than the culture of the high-volume chemical industry. It includes greater emphasis on quality and service," said Ralf Pfirmann, global business director, at the CPhI pharmaceutical ingredients trade show in October. "We're totally excited to be the business we always could be."
Like Clariant, Avecia, and Rhodia, Kemira also exited fine chemicals, selling its business to managers and the U.K.-based investment firm 3i in late 2004. Known as KemFine, the business subsequently doubled in size with the late-2005 acquisition of Avecia's fine chemicals operations in Scotland. Having its origins in larger companies, rather than struggling to grow from a small firm, gives KemFine big-company capabilities and a breadth of expertise, says Jamie Ferguson, the firm's vice president for pharmaceuticals.
KemFine has grown rapidly, Ferguson says, and today has annual sales of about $175 million. He notes that KemFine combines Avecia's development-stage and contract manufacturing activities with Kemira's primarily large-scale plants. "We now have a spread of assets across the whole of the development life cycle in pharmaceuticals," he explains.
"We can take advantage of when the pharmaceutical industry is very productive at the small-scale end to keep a manageable pipeline," Ferguson continues. Doing so allows a company to start with development-stage projects and grow with its customers, rather than compete for late-stage or already launched products where there are fewer opportunities. Along with the asset mix, diversification across agrochemical, pharmaceutical, and specialty markets reduces KemFine's exposure to lulls in any one sector, he adds.
Successful companies will have a range of technologies or ones in competitively advantaged niches, and they'll be close partners to their customers, not just suppliers, Ramakers believes. "You do that by building relationships and trust so that your customers want to take difficult or complicated chemistries out of their processes and leave it to the specialists." The further a fine chemicals firm can move up the pharmaceutical value chain, the better, he adds.
"Companies in Europe and the U.S. have an expensive manufacturing base, so they have to add more value to justify their prices," Ramakers says. "If the business goes to a level based only on price, they'll certainly lose to companies in China and to a lesser extent to those in India."
Industry participants and analysts are taking a cautious view toward the developing East-West interplay and how it will unfold. Asia already has become the major supplier of price-sensitive intermediates and APIs for generic drugs. Although Asia may be a threat, many Western fine chemicals producers are leveraging it to source their own low-cost intermediates.
As for those Asian companies having made Western acquisitions, some anticipate they will be successful if they retain key staff and maintain customer relationships. Others, however, believe executing new business plans will be difficult and suggest that cultural and other differences will make the East-West combination as unsustainable as the large conglomerate-fine chemicals dynamic proved to be. Yet others suggest it's just a matter of time before the cost advantage of producing in Asia diminishes (C&EN, April 17, 2006, page 24).
Despite the challenges ahead, some projections forecast good times for the fine chemicals market. Results of a business outlook survey conducted by the Synthetic Organic Chemical Manufacturers Association were upbeat. More than half of the 35% of SOCMA's members that responded considered the overall state of the market to be excellent or very good. Three years ago, only one-third of that year's survey respondents felt this way, and nearly 40% saw things as poor or fair. Most reported increased inquiries and sales in 2006 compared with 2005.
About half of the responders noted that technology introductions and changes in business strategy contributed to higher sales in 2006; emerging Asian companies were the leading competitive factor. Looking ahead to this year, an overwhelming 94% expect sales to increase. New product and technology introductions, product and process improvements, growth through acquisitions, and abandoning noncore offerings are approaches seen as driving profit growth in 2007.
CUSTOM MANUFACTURING is usually a growth business, industry analysts point out, but the past five years have been tough. A Frost & Sullivan research analyst anticipates 2006 sales growth for pharmaceutical fine chemicals companies of just 2-3%. "It is likely to be much better in 2007 and 2008 when target growth rates could be 5-8% because of the benefits of restructuring by pharmaceutical companies," he says, referring to plans by Merck, Pfizer, and Eli Lilly & Co. to reduce, close, or sell production capacity and potentially go to external manufacturers.
Aesica, like NPIL Pharma, took advantage of this situation when it acquired Merck's Ponders End, England, facility in late 2006. With it came a six-year supply agreement for intermediates and APIs worth up to $300 million. Aesica was formed in 2004 through a management buyout of BASF's Cramlington, England, site, which focused largely on bulk generic pharmaceuticals.
"The real test for us," says Aesica CEO Robert Hardy, "has been to move very quickly from being a supplier to the generics industry to growing our pharmaceutical contract manufacturing business and, at the same time, trying to become the supplier of choice to small and midsized pharmaceutical companies and biotechnology companies." For a company that started with just a few products and a list of no more than 20 customers, he adds, "it's fair to say that we've significantly increased both of those."
Given Aesica's success with the Merck deal, Hardy says he's still contacted by people trying to sell pharmaceutical production sites as part of their outsourcing strategy. What happens when or if this capacity hits the market, and there's a lot of it, is an open question. "Organizations like ours will not sit around with capacity 50% full like some of the larger pharmaceutical companies have been doing for quite a long time."
Overcapacity has plagued the fine chemicals industry for years, but manufacturers have been reluctant to engage in the wholesale plant closures that most observers agree are needed to balance supply and demand, especially in general purpose and non-GMP areas. "As long as growth in pharmaceuticals looked like it was 9-10% per year, and you thought you were going to be lucky with the projects you were working on, it was always only a 'matter of time' before your capacity utilization would improve," Dowpharma's Hyde says.
According to data from both SOCMA and Frost & Sullivan, there's about 25% excess capacity on average in the U.S. and European fine chemicals industries. Nevertheless, only 7% of responders to SOCMA's survey said they were likely to reduce capacity; about 84% said it was not likely. Instead, custom chemical firms are still banking on more business.
About 70% of respondents told SOCMA they expect to see more outsourcing by customers. Among these customers are small and virtual drug developers that lack their own production capabilities and Japanese firms now allowed to outsource (C&EN, May 15, 2006, page 29). Many industry insiders and analysts suggest that, if the large pharmaceutical companies choose to go outside, they will stick to preferred suppliers with proven track records rather than spread the business around.
Hyde cautions that production restructuring by the large drug companies may not lead to more outsourcing. He notes that many of these firms are struggling with the loss of products to generic competition and a dearth of new ones. Furthermore, the new products they do launch are often potent molecules that patients take in very low doses. If a drug company loses a high-volume blockbuster and closes production or keeps even part of it open for new, lower volume products, "contract manufacturers are no better off," he comments.
The ability of pharmaceutical companies to sell unwanted plants may be a good indicator of the prospects for the fine chemicals industry. "I think it's unlikely they will find buyers," Hovione's Villax believes. "The plants from a multinational drug company are not designed to be multipurpose, so it's not a good tool for people who need a lot of flexibility to give good service."
A lack of capability differentiation already contributes to the problem, because U.S., European, and Asian companies have very similar technology offerings, the Frost & Sullivan analyst says. In contrast, suppliers having specialized niche capabilities often report shortfalls in capacity and are adding more to keep up with demand. "Capacity utilization is a question of producers' portfolios," the analyst says, "and the high-potency and hazardous chemistry markets are growing around 10% per year."
Almac Sciences, known as CSS until June when Almac Group rebranded its five divisions under the Almac name, has a business strategy of linking such niche offerings. "We have very strong specialist capabilities in a number of areas in which customers have difficulty sourcing solutions, and where there's the possibility of connecting one to the other," explains David Moody, vice president for commercial operations. These areas include chiral building blocks, cytotoxics, radiolabeled compounds, and GMP peptides.
Almac Sciences connects with other Almac divisions and external partners to offer managed supply-chain services. For example, it may do custom synthesis and then work internally with Almac Pharma Services for formulation and drug product manufacturing and with Almac Clinical Services for packaging, labeling, and distribution of clinical trial supplies. To add a link in the chain, it just has joined with the Center for Pharmaceutical Science & Technology at the University of Kentucky, Lexington, for cytotoxic product packaging under sterile conditions.
In the chiral chemistry area, Almac also works with outside companies to offer the larger scale production capability it doesn't possess. "We look for the best manufacturing solutions, sited in the most appropriate assets, anywhere in the world," Moody says. It has toll manufacturing agreements with Excelsyn and KemFine and is exploring agreements with two suppliers in China and one in India. "We believe it's possible for a company that has the inventive strengths and specialist niche capabilities to augment them with low-cost manufacturing," he says.
"The strategy is to invent the solution in our facility in Northern Ireland and then have our customers decide where they wish to have materials manufactured," Moody explains, adding that Almac offers recommendations to help its customers make the best choice. Such a process, he cautions, must protect the intellectual property of both Almac and the customer. "Selecting the right partner is probably the hardest and most essential part to get right," Moody says.
THE PAST YEAR has been a good one for Almac Sciences, and the company has budgeted about 20% growth for 2007. "In the context of what's happening in the West, we're quite proud of that," Moody notes.
Similarly, Ampac Fine Chemicals (AFC), formerly Aerojet Fine Chemicals until a change of ownership in December 2005, has seen record sales. For the fiscal year ending in September 2006, sales were $92.3 million, a 42% increase over the previous year. Growth came from its energetic chemistry services, high-potency compounds, and new simulated moving bed (SMB) chromatography unit. "And 2007 is shaping up to be an extremely good year," says AFC President Aslam Malik, pointing to increased customer inquiries and more projects for compounds in Phase I and II clinical development.
"Our strategy is based on chemistry and engineering," Malik says, "and that strategy has worked well." Since opening in February 2006, the new SMB unit has been running at more than 97% uptime to process hundreds of metric tons of racemic feed per year. He expects AFC's production of high-potency products to exceed 2 metric tons in 2007, its diazomethane facility usage to be at a record high, and the company to continue to benefit from supplying azide-based intermediates for drugs such as Roche's antiviral drug Tamiflu.
AFC was one of 15 outside contractors that Roche signed up last year to help it produce Tamiflu (C&EN, March 20, 2006, page 10). Another was PPG Industries, which already had a relationship with Roche and was approached about producing the final Tamiflu intermediate, owing in part to a strong regulatory track record and history of environmental, health, and safety excellence, according to Luke Scrivanich, general manager of PPG's fine chemicals business.
PPG's technology strengths have been in phosgenation, chiral chemistry, and ozonolysis, but it decided to invest in the industrial-scale GMP azide capabilities required for the Roche project. The top-dollar equipment required to make high-potency compounds or do hazardous chemistries is generally a barrier to entry in these areas. "Fortunately, we had many systems in place because of our experience with phosgenation," which involves extremely hazardous chemistry, Scrivanich says.
PPG's fine chemicals unit tries to differentiate itself in the marketplace by being able to safely develop difficult chemistries and rapidly commercialize them. Although part of a major corporation, the unit "is pretty nimble" and benefits from having greater resources behind it, Scrivanich says.
Other large companies, such as BASF, DSM, Degussa, Lanxess, and Dow still maintain fine chemicals businesses. BASF expanded its custom manufacturing operations by acquiring the Swiss firm Orgamol in 2005, and it just added a team to support custom chemical services in North America. In late 2006, on the other hand, the company restructured operations in Minden, Germany, in response to tough competition in generic APIs and increased cost pressures from Asia.
Lanxess created Saltigo, a dedicated, "full service" custom chemicals subsidiary with about $520 million in annual sales, in late 2005 (C&EN, March 13, 2006, page 28). Despite cutbacks in jobs, production, and costs, Lanxess has been making selected investments. These include $13 million for multifunctional GMP capabilities that are to come on-line this year and another $40 million announced last month to modernize its plants and alter employee work rules.
Making Saltigo a stand-alone operation helped turn around a business that had been reporting substantial losses, Lanxess Management Board Chairman Axel C. Heitmann said last month. But even with higher capacity utilization and a steady increase in earnings, profitability is not yet satisfactory. The latest investments are designed to make the operation more competitive.
Degussa has been repositioning its fine chemicals business as well, cutting costs and selling its Canada-based Raylo Chemicals subsidiary to Gilead Sciences for $146 million. For Degussa, the sale is part of a growth strategy that involves shifting production from North America and Europe to Asia (C&EN, July 3, 2006, page 20). To do so, the company has taken a majority stake in Lynchem, a Chinese custom manufacturer, and has signed a long-term supply agreement with Hikal in India.
DSM, meanwhile, sold an API plant in Michigan to Albemarle (C&EN, Nov. 6, 2006, page 14). In biopharmaceuticals, it has shifted away from manufacturing, shutting down a Canadian plant and focusing instead on a joint venture with the Dutch biotechnology firm Crucell. The companies are developing and licensing Crucell's PER.C6 cell line for biopharmaceutical manufacturers. In November 2006, they opened the Perciva PER.C6 development center in Cambridge, Mass.
Likewise, Dowpharma has been developing its Pfēnex expression technology business for producing proteins. "The business is continuing to do extremely well, and 2006 was something of a banner year for us with three times the level of new project activity as in 2005," Hyde says. "We're continuing to sign commercial licenses at an increasing rate, and products made with Pfēnex entered human clinical trials in 2006." He expects strong growth to continue in 2007 and beyond.
"We certainly are focusing our energies on areas where we are differentiated and have a competitive advantage," Hyde says. For Dowpharma, these areas include chiral technologies, catalysts, and APIs. "We invested quite a lot in the API area in 2006 and are now looking for those projects to come to fruition," Hyde adds. The business also started up a new asymmetric catalyst manufacturing plant in Michigan in 2006 to support what Dowpharma calls "a growing pipeline of custom synthesis projects."
IN THE CURRENT environment, Hyde says, he sees significant resource and expertise advantages to being part of a large company. Such capabilities, he explains, "let you deal with pretty much every situation that might arise and build new differentiated positions in the marketplace." He does admit that there are times when "some big-company processes are perhaps a little bit slower than they might be in a smaller company.
"Everybody has to try to be agile at the moment," Hyde adds. "I think what we would all like to see is continued consolidation." Consolidation would allow for recovery in capacity utilization and in resource productivity. But with profitability as low as it has been, Hyde believes this will need to be what he calls a "cashless" consolidation involving creative business combinations rather than traditional cash deals.
"Companies would rather invest money in new growth and new business where they can make the returns than pay cash for acquisitions," he explains. "There's been a call for consolidation for a while, but it's been very slow happening, because it's difficult for companies to justify going out and buying a business in the current market with cash."
According to Frost & Sullivan's analyst, there are more than 500 pharmaceutical fine chemicals companies around the world with sales between $80 million and $120 million. Critical mass is a requisite for attracting pharmaceutical customers, he adds, and the fragmented market may see consolidation.
Although more change is afoot, some companies say the best strategy is staying the course. For nearly 50 years, Hovione's business has been based on a simple model that involves a lot of hard work on complex projects for demanding customers, Villax says. The company has more than 40 projects under way, thanks to an improvement in the number of late-stage projects still progressing and continued strength in early-stage ones.
Villax believes that business continuity in volatile times is a critical factor for success. Customers want to be assured of continuous supply during what can be long-term contracts from early-stage development through commercial launch. Given the custom manufacturing industry's recent upheavals, he says, customers should be asking a simple question: "What's the likelihood that a company is going to be around and that this business is important to it?"
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