Ensuring the Safety and Integrity of the World’s Drug, Vaccine and Medicines Supply : PART ONE
In anticipation of the upcoming G8 Summit this week I released a Policy Innovation Memo, Ensuring the Safety and Integrity of the World’s Drug, Vaccine and Medicines Supply – a Matter of Urgency for the G8/G20 Leaderships. This, and two subsequent blogs, will explain why this issue is urgent, how we addressed it at the Council on Foreign Relations, and what I conclude the G8 and G20 leaders can do to save millions of people from toxic, substandard, contaminated, mislabeled and dangerous drugs, medicines and vaccines.
[Photo: Chinese government steamrollers fake drug seizure]
Before her May 2009 swearing-in as Commissioner for the United States Food and Drug Administration (FDA), Dr. Margaret Hamburg did the sort of due diligence necessary to face interrogation by opposition party members in Congress. Traditionally the FDA had been a lightning rod for partisan controversy, and a target for anti-regulation politicians that favor free market solutions to safety issues. As she studied mountains of documents and listened to experts both in and out of government, Hamburg was struck by the dramatic changes globalization had wrought. In our conversations that spring, the fellow-New Yorker expressed mounting anxiety about the shrinking domestic pharmaceutical and vaccine share of the U.S. market, and soaring contribution from overseas. How, she wondered, could an almost 100 percent domestically-focused agency like the FDA protect the populace from what was rapidly becoming an overwhelmingly imported supply of drugs, vaccines, injectibles, medicines, supplements, and over-the-counter treatments?
Her questions could just as easily be asked by safety regulators in the United Kingdom, Germany, Canada, Brazil, Mexico, Singapore or South Africa. The same tidal wave of dubious importation now overwhelms regulators the world over.
The pace of change is staggering. In 2002, the FDA struggled to regulate 148,000 foreign-made pharmaceutical products: by 2010 that toll reached 400,000, which was nearly half of all finished drugs used in America. Even “made in America” generics, over-the-counter drugs, and pharmaceuticals are now made with foreign-derived components. By 2011, more than 80 percent of all active pharmaceutical ingredients (APIs) were made overseas, as were the majority of supposedly inert excipients used to formulate and stabilize medicines, and the capsules and containers into which compounds were sealed.
[From U.S. Food and Drug Administration, Global Engagement 2012, Washington, DC.]
Where bilateral political agreements are permitted, the FDA can make site inspections at chemical, extraction, and pharmaceutical production facilities overseas, but staffing and budget limitations limit such visits so that statistically any given non-U.S. factory is likely to be seen once every 13 years; versus American-based sites inspections once every two years.[i] By its own estimation, from 2002-2007, the U.S. FDA managed to inspect only 46 percent of legitimate foreign drug manufacturing sites and only gained entry to a handful of illegal producers over that time.[ii] Reliance on appropriate clinical testing of reformulated or all together new drugs has been challenging, as well. Again in the U.S. context this issue was nearly moot in 1990 when only 271 medicines that were eventually marketed in America were clinically tested overseas; however by 2008 that number soared to 6,485 compounds tested outside the country, but that were submitted for FDA licensing.[iii]Since 2008, clinical science has become a “landless frontier.”[iv]
If the United States FDA, with more than 11,500 employees, 335 of whom execute foreign drug-related inspections, and backed by strong legal mandates, can’t routinely get inside vitamin factories in Pune, heparin-making facilities in Guangzhou, Avastin storage facilities in Istanbul, or streptomycin factories in Lima, how can less well-funded, resource-poor regulators from poorer countries possibly protect their populations?[v] In 2005, the U.S., Western Europe and Japan produced 79 percent of the global supply of medicines, pharmaceuticals, and vaccines: by 2015 it is estimated that emerging market production will have soared and the old producers will have lost 12 percent of their combined market share.[vi] In part this reflects a shift in consumer markets. In the traditional bastions of pharmaceutical development, markets are projected to witness only modest expansion over the next three years, on the order of 3-to-7 percent, while China’s market will soar with 27 percent growth over the same time.[vii] Consumer markets are shifting, sites of clinical testing are moving, production is globalizing into a complex multinational web, and consumer demand has skyrocketed, and is expected to top $1 trillion in sales in 2015.[viii]
“The next five years will also see an accelerating shift in spending toward generics, rising to 39 percent of spending in 2015, up from 20 percent in 2005,” says business forecaster IMS Health.[ix] “On the other hand, share of patented brands which accounted for nearly 70 percent of global pharmaceutical spending in 2010 are expected to decline to 53 percent in 2015, on account of patent expiries, mainly in the developed markets.”
[From: IMS Health]
By 2020, Chinese companies will manufacture 13 percent of the global supply of finished pharmaceuticals, vaccines, and drugs; Indian manufacturers will make 12 percent, and Eastern Europeans 8 percent, for a total emerging market contribution of 43 percent of the world market.[x] The sharpest year-to-year percentage increase in demand and production overall, and specifically from China and India, is with vaccines. In large part thanks to the philanthropic investments of the Bill & Melinda Gates Foundation and the government of the United Kingdom, funding for childhood immunization in developing countries has soared since 2005, prompting creation of a vast international network of production and distribution. In its hasty expansion, that network is fraught with distribution problems that result in substandard immunization, and has spawned demand that has in some cases been met by criminal, false products.[xi] Some countries have, in response, created special laws for donated vaccines, stipulating safety and processing requirements.[xii]
A transformation is underway, dubbed by the FDA as “the great rebalancing,” reflecting the impact on drugs and medicines production of the larger, macroeconomic dispersal of power, labor, and manufacturing.[xiii]What is happening to drug-making in 2012 mirrors transformations in automobile manufacturing during the 1980s, computer and tech-making in the 1990s and outsourced professional services in the 2000s. There is, of course, one critical difference: dispersed manufacture and distribution of drugs has impact for human health. Every single aspect of drugs and vaccines research, development, testing, production, and sales is changing right now, and doing so at a breathtaking speed, while the nature of laws and agencies meant to ensure the reliability and safety of those medicines remains locked in antiquated modes that reflect quaint notions of local family-owned companies making products out of easily-inspected domestic factories.
[From Pew Health Group 2010]
In 2010 we began to study the drugs and vaccines safety problem at the Council on Foreign Relations with an eye toward global scale solutions that might:
- Improve the worldwide capacity to track, trace, and seize fraudulent, poisonous, substandard or spurious drugs, medicines, and vaccines that pose a threat to public health and safety;
- Ensure that pursuit of criminals or substandard manufacturers does not endanger access to life-sparing medicines for people living in poor countries, or poor residents of wealthier nations;
- Identify and address the bona fide public aspects of trade in counterfeited drugs and medicines;
- Encourage global-scale urgency and cooperation in this matter; and
- Operate within the difficult economic realities of the post-2008 Financial Crisis world.
We were greatly aided in our efforts by strong simultaneous drug safety analysis performed by the Pew Trust in Washington, D.C., London’s Chatham House, the U.S. General Accountability Office, OXFAM; Médecins Sans Frontières, the U.S. Institute of Medicine, and the American Enterprise Institute.[xiv] Over the course of 21 months, through confidential meetings and extensive literature searches, we learned that the world’s drug and vaccine supply is compromised; organized crime is increasingly engaged in alleged medicines production; regulators are overwhelmed or nonexistent; the World Health Organization lacks the necessary support and legal framework to engage effectively; and G8/20 involvement is imperative. The problem is global: solutions must also be worldwide in scale.
Our ultimate recommendations were delivered this month to the Group of Eight (G8). The brevity of that document belies the tremendous difficulty we encountered in finding common ground between key stakeholders, including the innovative pharmaceuticals industry, generic makers, API and excipient producers, attorneys, wealthy world government regulators, drug safety officials from developing and middle income countries, law enforcement personnel, humanitarian relief groups, and nongovernmental organizations representing health consumers in both rich and poor countries. Perhaps the greatest surprise we encountered over these two years was that the larger interests of some stakeholders often trumped efforts to reach practical compromise in pursuit of public health. We are aware that some participants in our Council on Foreign Relations process will object to statements contained both in the Policy Innovation Memorandum to the G8, and in this article: the divisions run deep.
NEXT BLOG POSTING: KEY FINDINGS ON THE SCALE OF DRUG SAFETY HAZARDS
[i] Government Accountability Office (GAO). Drug Safety: Preliminary Findings Suggest Weaknesses in FDA’s Program for Inspecting Foreign Drug Manufacturers. Washington, DC: Government Accountability Office, November 2007. http://www.gao.gov/new.items/d08224t.pdf.
[ii] U.S. Food and Drug Administration. A Special Report: Pathway to Global Product Safety and Quality. Washington, DC: U.S. Food and Drug Administration, July 2011. http://www.fda.gov/downloads/AboutFDA/CentersOffices/OC/GlobalProductPathway/UCM259845.pdf.
[iii] Bartlett DL and Steele JB. Deadly Medicine. Vanity Fair 2011; 57-63 and 113-114. http://www.vanityfair.com/politics/features/2011/01/deadly-medicine-201101.
[iv] Bianco, P. Science, the landless frontier. Longitude 2011; 13: 25-32.
[v] U.S. Food and Drug Administration. How Many People are Employed by the FDA and What Areas Do They Work In? http://www.fda.gov/AboutFDA/Transparency/Basics/ucm213161.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=how%20many%20people%20are%20employed%20by%20the%20FDA&utm_content=1; GAO. Drug Safety. http://www.gao.gov/new.items/d08224t.pdf; Government Accountability Office. Food and Drug Administration: Overseas Offices Have Taken Steps to Help Ensure Import Safety But More Long-Term Planning is Needed. Washington, DC: Government Accountability Office. http://www.gao.gov/assets/320/310614.pdf.
[vi] IMS Institute for Health Informatics. The Global Use of Medicines: Outlook Through 2015. IMS Market Prognosis 2011. http://www.expresspharmaonline.com/20120115/market02.shtml.
[vii] The Pharmaceutical Market Outlook to 2015: Implementing innovative, long-term strategies for sustainable future growth. Business Insights 2005. http://www.researchandmarkets.com/reports/302088/the_pharmaceutical_market_outlook_to_2015.
[viii] IMS. The Global Use of Medicines.
[x] U.S. Food and Drug Administration. A Special Report.
[xi] Institute of Medicine. Ensuring Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad. Washington, DC: National Academies Press, 2012. http://www.iom.edu/Reports/2012/Ensuring-Safe-Foods-and-Medical-Products-Through-Stronger-Regulatory-Systems-Abroad.aspx.
[xii] National Agency for Food and Drug Administration and Control. Guidelines for Registration of Regulated Products, Volume 2. Abuja, Nigeria: NAFDAC, 2011.
[xiii] U.S. Food and Drug Administration. A Special Report.
[xiv] After Heparin: Protecting Consumers from the Risks of Substandard and Counterfeit Drugs. Washington, DC: Pew Health Group, 2011; Clift C. Combating counterfeit, falsified, and substandard medicines: Defining the way forward? London, UK: Chatham House, 2010; Government Accountability Office. Drug Safety.; Government Accountability Office. Food and Drug Administration.; Oxfam. Eye on the Ball: Medicine Regulation – Not IP Enforcement – Can Best Deliver Quality Medicines. 143 Oxfam Briefing Paper 2011.http://www.oxfam.org/sites/www.oxfam.org/files/eye-on-the-ball-medicine-regulation-020211-en.pdf; Medecins Sans Fronteriers. Counterfeit, Substandard, and Generic Drugs.http://www.msfaccess.org/content/counterfeit-substandard-and-generic-drugs; IOM. Ensuring Safe Foods; Bate R. PHAKE: The Deadly World of Falsified and Substandard Medicines. Washington, DC: AEI Press, 2012.