Throughout 2010, most companies with a rating headroom (A+) such as GSK, Roche, Sanofi- Aventis, and Bristol-Meyers Squibb pursued opportunities to broaden product offerings and expand geographically along with their R&D programmes. Nevertheless, such defensive strategies are likely to lead to a decline in profitability over time due to the rapid increase in the cost of prescription drug containment by regulatory agencies, health authorities, and third-party payers, as well as the near- term drug patent lapses dampening current restructuring and ‘efficiency’ efforts. High-profile managers of all of those companies are therefore facing increasing challenges such as responding to higher demand to deliver larger profits from increasingly smaller promotional budgets in the midst of a very turbulent environment: the world pharmaceutical market was worth an estimated €484 130 million ($663 500 million) at ex-factory prices in 2007. North America accounted for 45.9% of world pharmaceutical sales against 31.1% for Europe, but the European market outpaced the US market in terms of growth (6.7 vs. 4.2%).