The heparin problem arose less than four months after the US Government Accountability Office (GAO) presented testimony highlighting the deficiencies in FDA's oversight of foreign drug manufacturers. The active pharmaceutical ingredient in Baxter's heparin was supplied by Changzhou SPL in Changzhou, China, which is partly owned by Scientific Protein Laboratories LLC (Waunakee, WI). GAO noted that FDA "does not know how many foreign establishments are subject to inspection," and that its two principal internal databases counted vastly different numbers of foreign establishments (3000 in one case, 6800 in another). The GAO report estimated that FDA was inspecting only about 7% of foreign establishments deserving inspection each year, meaning it would take more than 13 years to visit each site once. The report noted other problems, including the need to preannounce FDA inspections of foreign facilities and the lack of translators on FDA inspection teams.
In fact, GAO noted, FDA does not have the authority to compel foreign establishments to allow it to inspect their facilities. Further, foreign drug establishments making product for the US market do not have to be inspected every two years, as domestic requirements must be. FDA's authority is currently limited to inspecting imported drugs and preventing their entry into the US. There is now a movement in Congress, backed by the Bush administration, to give FDA more explicit responsibility for imported drugs.On the supply-chain learning curve
Baxter and SPL's heparin problems, and the difficulties FDA has keeping up with foreign establishment inspections, represent just some of the issues that pharmaceutical companies are likely to encounter as they source key ingredients and intermediates from countries such as China and India. Pharmaceutical supply chains are getting longer and more complex; companies are not only geographically farther from their suppliers, they are transactionally farther as well, because they increasingly depend on their primary suppliers to source intermediates and other inputs used to manufacture the products they are ultimately purchasing. This is a far cry from just a few years ago when vertically integrated pharmaceutical companies controlled much more of the supply chain and manufactured most active ingredients and late-stage intermediates in-house.
The learning curve for complex sourcing relationships has been a long one in most industries, not just pharmaceuticals. Companies that have sought to outsource more of the value chain almost invariably have found that their internal systems are not up to the task and that they must have greater involvement with their suppliers to effectively integrate them into their supply chain. For example, when Boeing developed its new 787 Dreamliner aircraft program, it decided to outsource the production of many of its components to suppliers around the world. Now, it has had to delay delivery of the Dreamliner several times because it failed to effectively integrate those suppliers into its scheduling and engineering systems. In addition, the suppliers have not been able to deliver their components on time and in sufficient quantities. When the automobile companies began seriously outsourcing more than 10 years ago, they found that they had to establish stringent quality standards and specifications and invest in training their suppliers in continuous improvement and quality control practices before they could meet these standards.
The globalization of supply chains is creating new political, logistical, and scientific challenges for the pharmaceutical industry. Establishing inspection programs of foreign establishments, for example, will require agreements with foreign governments to allow FDA to exercise some oversight authority over manufacturers in their countries. That will be especially tricky with countries such as China, where there is no history of mutual recognition and cooperation such as exists with European governments.
There will be technical and scientific issues as well. For instance, while investigating the heparin recall, FDA found that the heparin API supplied by SPL to Baxter contained a heparin-like compound that was not heparin but reacted like heparin in traditional analytical tests. FDA did not immediately establish a causal link between the contaminant and the adverse events but issued guidelines for additional analytical tests to identify the foreign substance.
In fact, comprehensive analytical testing is likely to become a more important link in pharma's global supply chain and in FDA's efforts to maintain the safety of human and animal products. This will become a major opportunity for contract analytical labs, especially the worldwide laboratory networks run by companies such as SGS and Intertek, which already have extensive consumer-testing operations and dozens of facilities around the world. Other contract analytical services providers have been slow to establish operations in India and China but are likely to move more deliberately in the near future.
The explosive growth in offshore sourcing by the pharmaceutical industry is a relatively recent phenomenon and is directly related to margin pressures felt by pharmaceutical companies resulting from efforts by governments and health insurance providers worldwide to slow the growth of healthcare expenditures. Offshore sourcing has grown so quickly that it has overwhelmed the systems put in place by industry to maintain product quality and safety, and it has afforded no room for "on-the-job" learning. Regulatory agencies and pharmaceutical companies will have to devote more resources to anticipating potential supply-chain risks and implementing mechanisms to prevent them.
Jim Miller is president of PharmSource Information Services, Inc., and publisher of Bio/Pharmaceutical Outsourcing Report, tel. 703.383.4903, fax 703.383.4905, [email protected]