Overseas manufacturing has brought benefits in terms of lowering the cost of producing APIs and excipients used in US drug products, and of many finished drugs sold the US. The dark side of the arrangement, and the one that worries consumers, manufacturers, and regulatory agencies, is that quality control becomes very difficult when supply chains involve the routing of thousands of products through manufacturers, packagers, and distributers dispersed around the world. The worst-case scenario, where adulterated ingredients end up in finished drug products was realized in late 2007, when adulterated heparin sourced from China caused adverse drug reactions and the deaths of some patients.
The PEW Charitable Trust released an extensive report this month, using the heparin crisis as a jumping-off point for examining the global supply chain. The report provides a thorough examination of the global supply chain, and contains sections that speak to the responsibilities of US drug distributors and regulatory agencies in ensuring that medicines sold in the US are safe and effective.
The report begins by summarizing the globalization of pharmaceutical manufacturing, outlining the problems with quality-management strategies currently in place, and making recommendations for a more secure supply chain. The recommendations include:
• requiring that 21st-century quality systems be implemented to protect drug safety through statute and regulation
• improved industry control of its control of contract manufacturers and suppliers
• Enhanced documentation and transparency of the upstream manufacturing supply chain
• Improved testing standards by improving testing methodologies and by continual updating of public testing standards.
These recommendations come down heavily on the companies that buy drug components outside the US to be responsible for ensuring the purity of their ingredients. The second section of the report, however, is devoted to FDA, and examines three main areas where agency oversight is hampered: inspections, data sharing, and enforcement. The recommendations for improving FDA oversight are:
• Increase oversight of overseas manufacturing
• Ensure adequate resources
• Improve infrastructure and tracking systems
• Strengthen oversight of drugs and bulk drug substances at import
• Ensure that authorities exist to to fulfill its mission
• Strengthen enforcement ability with tougher penalties and clearer accountability for industry
• Improve access to information from other regulatory bodies and industry.
The report does mention the elephant in the room, that is, despite having broad responsibility for ensuring the safety of food and medicines in the US, FDA is operating under fiscal constraints. To highlight these challenges, the report notes that although Congress passed 123 laws between 1988 and 2007 requiring FDA action, the agency was only allocated a 9% staffing increase during that time. FDA is struggling to fulfill its regulatory mandate at home, and simply doesn’t have the resources to be the world’s manufacturing watchdog. Until such time as GMP standards are uniformly applied and enforced throughout the world, ensuring drug purity is a task that will have to be shared by government and industry.