FDA Enforcement Priorities Include Globalization Threats

FDA will overhaul its enforcement approach to reflect the impact of globalization by partnering more with foreign counterparts, streamlining inspections, recalls and emergency responses and using stiff criminal sanctions to deter noncompliance, agency officials say.

FDA will expand enforcement beyond U.S. borders in 2012 to address developing safety threats from globalization, top agency officials say.

“We have to shift to a more global agenda” that addresses the emerging regulatory environment in which national borders are less relevant to product safety than in the past, said Howard Sklamberg, deputy associate commissioner for regulatory affairs in FDA’s Office of Regulatory Affairs, who spoke at the Food and Drug Law Institute’s Enforcement, Litigation and Compliance Conference Dec. 6.

FDA will overhaul its enforcement approach to reflect the impact of globalization by partnering more with foreign counterparts, streamlining inspections, recalls and emergency responses and using stiff criminal sanctions to deter noncompliance, Sklamberg said.

More Foreign Inspections Slated As Imports Rise

FDA will streamline and conduct more inspections to address the enormous challenges posed by the rapidly growing volume of food and drug imports and the increasing complexity of the global supply chain, Sklamberg said.

On average over the last seven years, food imports increased 10% annually and pharmaceutical product imports increased nearly 13% annually, he said.

Sklamberg predicted imports will continue to increase 5% to 15% through 2015 – nearly tripling the number of FDA regulated products imported since 2007.

In addition, the number of foreign drug manufacturers registered with FDA also increased nearly seven-fold since 2002 when fewer than 500 foreign firms were registered. In 2010, nearly 3,500 foreign firms registered with FDA, Ilisa Bernstein, acting director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research, said during the FDLI conference.

As the number of registered foreign firms increases, so does the number of warning and untitled letters FDA sends about international drug quality issues, she said. In 2005, the agency sent just two such warning letters and one such untitled letter. These climbed to 19 warning letters and four untitled letters in fiscal 2010, she noted.

FDA Enforcement Priorities

FDA plans to address increasing threats from globalization in 2012. The agency will:

• Address increasing supply chain threats
• Ensure good manufacturing practices compliance
• Ensure commitment to quality at the local and systems level
• Ensure quality systems in clinical trials
• Remove unapproved drugs from the market
• Conduct more foreign inspections
• Streamline case review procedures
• Improve recall communications and search engines
• Work more closely with regulatory partners abroad
• Prioritize follow-up actions, including those related to warning letters
• Implement a warning letter close-out process
• Implement the Food Safety Modernization Act

FDA will increase foreign inspections in response to the growing number of manufacturers abroad, Sklamberg said. He noted the agency already increased foreign food facility inspections from 354 in fiscal 2010 to 637 in fiscal 2011 with more in the pipeline.

FDA Seeks International Partners

However, the demand to conduct more foreign inspections – a total of 19,200 in the next five years – could outpace FDA’s budget and resources, Sklamberg cautioned.

“We are trying to do a lot more … with not many more resources,” he said, adding one way FDA is inspecting “smarter” is through partnerships with its international counterparts.

“We can’t be everywhere, so we have to look at how we can move towards relying on our international partners and regulators and so we are doing a number of different pilots right now and doing some joint inspections – particularly with Australia, Europe and Canada,” Bernstein said.

For example, she said, FDA, the European Medicines Agency and the Australian Therapeutic Goods Administration shared inspection information that allowed them to reduce duplicate site visits during a two-year pilot that ended in December 2010. The pilot was so successful the agencies plan to expand the partnership to other members (Also see "Collaboration On Foreign Inspections Helps FDA Improve Resource Allocations" - Pink Sheet, 15 Aug, 2011.).

FDA also “is really excited about” joining the Pharmaceutical Inspection Cooperation/Scheme (PIC/S), Bernstein added. She explained 39 countries share inspection information and “leverage learnings” through the cooperation.

FDA also is partnering with EMA to develop a new risk model to identify and inspect clinical research sites, Bernstein said.

Globalization Increases Supply Chain Threats

Globalization also threatens food and drug safety by creating more links in the supply chain that are vulnerable to threats of counterfeit, diversion and cargo theft, Sklamberg said. Addressing these risks is another FDA enforcement priority, he said (Also see "Threat Of Adulteration For Profit Grows With Globalization Of Supply Chain" - Pink Sheet, 13 Oct, 2008.).

CDER’s Office of Drug Security, Integrity and Recalls will look at global supply chains “all the way from the lifecycle approach of the products starting with the inactive and the bulk ingredients, APIs all the way through the manufacturing, production, distribution and total product that reaches the patient,” Bernstein said.

As part of this effort ODSIR is “focused a lot on cargo theft,” and working with stakeholders to identify best practices to prevent thieves and stop stolen products with compromised integrity reentering the marketplace, Bernstein said (Also see "FDA cargo thief warning" - Pink Sheet, 3 May, 2010.).

Likewise, she added, the office is developing standards for tracking and tracing drug packages through the supply chain and is “hoping to issue something in the near future.”

The office is teaming with international partners to block diversion and counterfeiting. For example, it participated in Operation Pangea IV with 81 other countries which targeted 997 websites illegally selling unapproved or misbranded drugs to U.S. consumers. The operation was part of the International Internet Week of Action, and resulted in warning letters going to more than 700 websites and the suspension of nearly 600 sites.

FDA also is looking for ways to more quickly and efficiently remove not only intentionally compromised products from the market, but also products that are unintentionally compromised through manufacturing, packaging or other points in the process.

“We will comprehensively look at our recall process to see, are there things we can do in it that are simply more efficient, are there better ways we can communicate with the public so the public can know more quickly what the status is of a recall, and ways we can work more efficiently with a firm that is doing a recall in terms of audit checks and other parts of the recall,” Sklamberg said.

FDA Will Use Enforcement For Deterrence

FDA plans to clarify concerns in warning letters and add more teeth to the process in 2012, Sklamberg said.

He recognized that warning letters do not have the force of law, but urged firms to address problems in the letters in a timely fashion, or else the agency will take enforcement action. To improve compliance with letters, the agency plans to conduct follow-up inspections and work “with firms in the warning letter process in a way that firms can understand what FDA wants,” he said.

He also reminded industry that FDA no longer issues repeat warning letters. So if a firm adequately addresses a problem in a warning letter, but it occurs again, the agency could take enforcement action.

FDA also will not hesitate to make examples out of firms and individuals involved in serious criminal situations.

Sklamberg said, “When we have an issue with a firm or generally a public health issue what we want is not to just deal with this situation immediately, but make sure it doesn’t happen again. We can do that through regulation, outreach and also through deterrence. And for the really bad situations that would involve criminal law,” FDA wants to send a message “not just to the people who themselves are arrested or charged, but to folks looking at that.”

For example, FDA underscored the importance of GMP compliance recently when it went after the owner and two managers at Quality Formulation Laboratories and [American Sports Nutrition Inc.] Recently, all three were sentenced to about three years in prison (Also see "Enforcement In Brief" - Pink Sheet, 5 Dec, 2011.).

To help drive that message home, FDA plans to take enforcement action more quickly by streamlining its review process, Sklamberg says. “Sometimes our enforcement actions take time, and they should. A lot of them are hard. The science is hard. Making sure we are being consistent is hard. And we have to think through this. But they shouldn’t take years. … We are trying to make it as quick as possible so that we deal with not just the public health emergency, but send that message as quickly as possible.”