The FDA announced yesterday that it had taken steps to mitigate shortages of two cancer drugs, Doxil and preservative-free methotrexate. Doxil, a drug used to treat ovarian and other cancers, has been in short supply for months, after manufacturing problems shut down the drugs' sole U.S. plant. The FDA will temporarily allow importation of Doxil from an Indian manufacturer, a move that is expected to effectively end the shortage.
For preservative-free methotrexate, a critical cancer drug for pediatric acute lymphoblastic leukemia (ALL) and bone cancer, the FDA has asked other pharmaceutical companies to step in to fill demand after a major supplier, Ben Venue, shut down a plant making the drug for "maintenance and requalification of equipment."
The FDA reports that it has prevented nearly 200 shortages in 2011 thanks to advance notice from manufacturers, but 280 drugs remain in short supply. Short term fixes are welcome. Long term fixes are harder to come by.
The U.S. market strongly encourages substitution of branded drugs by generics immediately after a drug loses patent protection. For very profitable drugs (like statins) generic companies will rush in to fill the vacuum, slashing prices and saving consumers and insurers billions in annual drug costs. For high demand, high profit generics (and branded drugs), shortages will be few and far between.
But for other medicines, like sterile injectable drugs, which have high manufacturing costs and narrow profit margins, fierce price competition may eventually drive all but one or two manufacturers from the market. And when there are only one or two suppliers, it creates the opportunity for drug shortages when unexpected manufacturing problems at a single plant can place thousands of lives in jeopardy.
One solution, offered by the FDA's Sandra Kweder in an interview yesterday, is for "a shift in the industry to assuring good manufacturing practices to prevent finding themselves in a critical juncture where they have no choice but to shut down."
This, however, puts all the blame in the wrong place. By all means, companies should comply with the current Good Manufacturing Practices required by the FDA, and find ways to share information to help prevent or alleviate the effect of drug shortages.
But perverse Medicare price controls, just-in-time inventory supply practices at hospitals, reverse auctions by Group Purchasing Organizations for filling generic drug contracts, tougher FDA manufacturing and inspection standards for domestic companies (which can raise costs), and increased global competition from low-cost suppliers in India and China has created something of a "race to the bottom" in the generic drug market.
In this environment, quality (but higher cost) manufacturers may (rationally) exit the market to focus on higher margin products. And the few low cost suppliers that remain for complex drugs like sterile injectables may not be able to ensure the integrity of their manufacturing and supply chain over time at a rock-bottom price.
In other words, if private and public purchasers insist on driving prices below a sustainable level, drug shortages may become an endemic feature of the U.S. generic drug marketplace - as they have over the last several years.
You can find good articles on the problem (and potential solutions) here, here, and here (by yours truly).
Funding constraints, hopefully addressed by the new generic drug user fee agreement, have limited the FDA's ability to conduct timely inspection of foreign plants, posing a potential safety risk for patients. It also creates an imbalanced playing field for U.S.-based companies that are inspected more frequently and adhere to higher, more expensive safety and quality standards. In this environment, quality American manufactuers can't compete on price.
Until China and other developing countries raise their manufacturing standards to match those of the U.S., a market-based solution that would supplement the FDA's efforts would be for industry to work with regulators to create a voluntary third-party certification system for manufacturing standards and supply chain integrity for contractors based in developing countries where regulatory standards don't meet those of the FDA or EMA. This approach would mimic independent non-profit organizations like the Joint Commission, which certifies hospital quality, for the global pharmaceutical manufacturing and supply chain. Something like this may already be in the works at Rx360.
Under a certification system, companies that submitted to regular third party inspections and other quality measures would receive a "seal of integrity" that they met or exceeded established regulatory standards.
Generic drug purchasers could still opt to buy from the lowest bidder, but they would do so at their own (and their patients') risk. Third party certification of supply chain integrity would help counteract the "race to the bottom" in generic drug pricing without intrusive government regulation by sending better market signals about manufacturers' commitment providing a dependable supply of the highest quality medicines - not just the cheapest.