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FDA must increase inspections of foreign API manufacturing facilities as more production moves offshore.
The quality and safety of drugs is critical, and this fact is why the Synthetic Organic Chemical Manufacturers Association (SOCMA) is calling for more frequent inspections of foreign facilities manufacturing active pharmaceutical ingredients (APIs). Much of our nation's APIs come from facilities outside our borders and outside the normal inspection processes. The US Food and Drug Administration is required to inspect foreign facilities every two years, but even FDA's data shows that while it may perform a premanufacturing inspection, the agency rarely follows up on these inspections once a facility has begun manufacturing.
FDA's enforcement regime is woefully inadequate. The agency is not allowed to enter into a foreign facility without an invitation. FDA has partnerships with other nations allowing it to perform inspections, but typically must give advance notice of when it will conduct an inspection. FDA is only allowed to perform inspections at facilities approved by the foreign government. Inspections of foreign facilities are shorter, and many times, inspectors must deal with language barriers.
In our White Paper released last year, SOCMA called on FDA to increase foreign inspections and classify foreign manufacturing as a significant risk factor in the formula used to determine FDA's inspection priorities (1). Congress also needs to get more involved and look at our nation's inspection regime. At the very least, Congress needs to improve FDA's funding for foreign inspections to allow the agency to hire more inspectors and provide them with a travel budget.
Since every federal agency, however, "needs" more money, FDA must consider alternative methods. FDA must get countries to adopt enforcement regimes based on the US or European model, complete with transparency. Instead of attempting inspections at every facility in the world that exports to the United States, FDA should work with nations' internal authorities to train inspectors and set up a system that ensures API safety.
Under such an approach, FDA would be able to spot audit API manufacturers targeting products meant for the US market. We acknowledge that this approach is not an ideal solution as the US cannot be the inspector to the world, but FDA has the burden of protecting our nation's drug supply, a burden it is currently nowhere near fulfilling.
In 2006, 1222 inspections were undertaken at domestic manufacturing facilities, compared with only 200 inspections in India and China during the past seven years combined despite the huge increases in manufacturing in these nations (2).
As globalization continues to force companies to compete with the lowest cost manufacturing, more and more manufacturing is being outsourced to overseas manufacturers. This manufacturing falls under less rigorous or nonexistent inspection processes. FDA is by default creating two different enforcement regimes. A domestic one, where manufacturers expect and receive a visit by a FDA official every two years, and a second one for outsourced APIs that are almost never uniformly inspected.
These different enforcement regimes create economic conditions putting domestic manufacturers at a distinct disadvantage. Companies operating outside of a vigorous inspection regime have no incentive to ensure the quality and safety of their products. In such an environment, US manufacturers cannot compete, resulting in cutbacks, layoffs, and closures. More and more manufacturing is sent offshore, resulting in an even greater likelihood for mishandled and poorly made APIs to reach consumers.
While we are beginning to see industry and the public notice our nation's woeful inspection processes, it is mainly in food safety and almost completely as a result of scares surrounding pet food and toothpaste contamination. APIs are sadly, not in the fast lane. Congress, industry, and consumers need to demand more accountability from the system. It is only a matter of time that a "scare" becomes a reality.
1. "Uneven Enforcement Leads to Subpar Drugs and National Security Risk," Synthetic Organic Chemical Manufacturers Association (Washington, DC) and European Fine Chemicals Group (Brussels), Aug. 2006.
2. M. Kaufmann, "FDA Scrutiny Scant in India, China as Drugs Pour Into US," Washington Post, p. A1, June 17, 2007.
Synthetic Organic Chemical Manufacturers Association and European Fine Chemicals Group Unite on Foreign Inspections
The Synthetic Organic Chemical Manufacturers Association (www.socma.org) (SOCMA, Washington, DC) and the European Fine Chemicals Group (www.efcg.cefic.org) (EFCG, Brussels) are two organizations that have taken an active role in calling for an increase in inspections of foreign manufacturing facilities of active pharmaceutical ingredients (APIs).
SOCMA is the US-based trade association representing chemical batch and custom manufacturers, which includes contract manufacturing organizations producing APIs and intermediates to the pharmaceutical industry.
EFCG, which was formed in 2004 to address the issue of growth and competitiveness among European fine chemical companies, is part of the European Chemical Industry Council (Brussels www.cefic.org the European trade association representing chemical manufacturers. EFCG consists of 200 companies and six national trade associations representing European fine chemical companies.
Last fall, SOCMA and EFCG issued a joint position paper on the need for more inspections of foreign API manufacturing facilities (1). The move followed the 2006 submission of a citizen petition to FDA by SOCMA's Bulk Pharmaceuticals Task Force (BPTF), which had asked the agency to increase inspections of drug-manufacturing facilities located outside of the United States. The petition may be found here www.socma.org/PDFfiles/NewsReleases/BPTF_Citizens_Petition_Foreign_InspectionFINAL.pdf
In filing the citizen's petition, SOCMA asserted that nearly half of all drugs marketed in the United States are produced or manufactured in foreign facilities, but that the vast majority of FDA inspections occur domestically.
The petition outlined recommendations for improving FDA's ability to reduce the risks from drug products imported into the US. "Currently, the FDA inspects facilities according to a risk-based formula that weighs a variety of factors," said SOCMA in a 2006 release. "Being a foreign facility is not a factor in the formula." Based on that finding, the BPTF made three recommendations in the petition:
The EFCG also has taken an active role in is raising concerns over the preparedness of the European Union and European national regulatory authorities in implementing recent EU legislation, EU Directives 2004/27 and 2004/28, which became effective October 2005. The laws require that all medicines marketed in the EU be made with APIs that comply with the harmonized GMP standard ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. (www.ich.org/cache/compo/276-254-1.html. EFCG) EFCG has drawn attention to the need for increasing foreign-inspection resources and improving enforcement measures by EU and national regulatory authorities in the EU (2, 3).
These measures come as the supply patterns of APIs into the EU have shifted from domestic sources to offshore sources. European producers supplied more than 80% of APIs into Europe in the 1980s, but now supply less than 30% of APIs coming into Europe (3). In the 1980s, India and China accounted for less than 10% of API supply into Europe, but now supply more than 70% of APIs into Europe (3)
In their joint position paper, SOCMA and EFCG called for increased foreign inspections based on the changing pattern of API supply into the US and EU. The joint statement specified that the level of foreign inspections has not kept pace with changing supply patterns. "In 2005, FDA conducted 163 inspections of foreign API manufacturers, of which 14 (9%) of the API inspections were in China, 23 (14%) were in India, which is not proportional to the quantity of API being imported," said the SOCMA-EFCG statement. The position paper estimates that around 80% of the volume of APIs that are used to make the drugs in the EU and US come from abroad (1).
—Patricia Van Arnum, senior editor, Pharmaceutical Technology
1. "Uneven Enforcement Leads to Sub-par Drugs and National Security Risk," European Fine Chemicals Group (EFCG, Brussels, Belgium) and the Synthetic Organic Chemical Manufacturers Association (SOCMA, Washington, DC), www.socma.org/PDFfiles/bptf/EFCG-SOCMA_common_position_paper.pdf accessed Aug. 1, 2007.
2. G. Villax and C.Oldenhof, "Global API Sourcing: What is Next for Suppliers to the European Union," Pharmaceutical Technology Sourcing and Management 2 (7), e10–e19 (2006), www.nxtbook.com/nxtbooks/advanstar/ptsm0706/
3. P. Van Arnum, "The EFCG Looks to Add Muscle to New European Legislation," Pharmaceutical Technology Sourcing and Management2 (3), e4–e20 (2006), http://www.nxtbook.com/nxtbooks/advanstar/ptsm0306/