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Susan Winckler was chief of staff to the FDA Commissioner from 2007-2009. In 2007, she led the FDA’s medical product negotiation with China’s then-State Food and Drug Administration, resulting in the Product Safety Memorandum of Agreement to enhance the safety of food, drugs, medical devices, and animal feed traded between the two countries. Under this legally binding agreement, both nations agreed to notify one another as soon as they discover a circumstance — such as a product recall — that could endanger public health.
Negotiations on the agreement took place against a backdrop of public health incidents associated with imported food and medical products from China. Earlier that year, hundreds of cats and dogs in the United States died or experienced kidney failure after eating pet food containing an ingredient from China that had been contaminated with the industrial chemical melamine used to simulate higher protein content. Also, that year, the FDA had issued import alerts on fish and toothpaste imported from China after finding traces of antibiotics and antifungals in the fish and the poisonous chemical diethylene glycol in the toothpaste.
Having the agreement in place was helpful as early as January 2008, when the FDA was confronted with reports that dialysis patients were experiencing severe allergic reactions after receiving the blood thinner heparin. The FDA would ultimately track the source of the adverse reactions to a contaminated raw component of heparin produced in China. The component had been adulterated with counterfeit product, over-sulfated chondroitin sulfate, that mimicked the real drug.
China itself confronted a far-ranging food safety scandal involving melamine in milk and infant formula in 2008, affecting over 300,00 children in China. Those cases prompted the FDA to issue an import alert to ensure imported dairy products from China that appeared adulterated did not reach U.S. consumers.
Winckler is currently CEO of the Reagan-Udall Foundation for the Food and Drug Administration, which facilitated the Operational Evaluation of FDA’s Human Foods Program and the subsequent evaluation and report submitted to FDA Commissioner Robert Califf on December 6, 2022.
The staff from the Office of Global Policy and Strategy recently spoke with Winckler about her experiences in responding to those public health incidents in 2007 and 2008, how they prompted the establishment of the foreign offices, and how this experience influenced her work on Reagan-Udall’s evaluation of the FDA’s human foods program.
What was it like working at the FDA during a period of significant public health product safety issues like melamine and heparin?
Every day at the FDA is busy and interesting, but there is always something that you can’t predict. We found ourselves in late 2006 into 2007, and most of 2008, experiencing an increased number of safety issues from products coming from outside the United States. These issues highlighted a gap that needed to be addressed to better navigate those issues, such as understanding the local dynamics and customs in foreign countries or being able to send investigators to another country to inspect facilities. Melamine, for example, first appeared in pet food. After tracing those products to ingredient suppliers in China, it took quite some time to get visas to send investigators to China. With the human safety issues in heparin, access for investigators was faster, but we still had a lack of visibility into current events and market dynamics outside of the United States. It was striking for the FDA to see how much of the agency's responsibility was affected by activity happening outside of the borders of the United States.
The questions that persisted were less about where problems were emanating from and more about what's going on in the different regions around the world. Compounding those questions were factors such as, can we have a presence in those different regions? Do we understand the local norms and practices of what's happening in each locale?
These issues, and the questions they raised, convinced FDA Commissioner Andrew von Eschenbach and the leadership above the FDA, i.e., at HHS [Department of Health and Human Services] and the White House, to say we need to do more. To better serve the American public and protect and promote their public health, we need to have a better understanding and a stronger presence near the industries that are located outside of our borders and grow our relationships with those colleague regulators who are engaged in activities similar to the United States.
Were there other factors that played a role in these decisions?
The volume and variety of FDA-regulated products crossing the border was certainly a factor, as well as a recognition that quality and regulatory compliance are built into products, not addressed at the end of a processing or manufacturing cycle. Building a culture of quality and safety requires interaction with industry, such as clearly explaining the “what” and “why” of regulatory requirements. When those processes take place beyond the U.S. borders, the FDA’s engagement needs to occur beyond those borders as well.
The FDA first learned about the melamine contamination in March 2007, heparin was in March 2008, and then the China office was established by November 2008. That happened lightning-fast. How were you able to move so quickly on those things?
A couple of different things contributed to that. You had engaged leadership at both the FDA level and the HHS level. In addition, the President issued an executive order saying we would need to know more about import safety, writ large, and the FDA was an essential component in looking at import safety across all products that come into the United States.
Also, I think the profound toll of melamine – both animal melamine and melamine in dairy containing products – were significant. And in the contamination in pet food there was a renewed sense in the United States of where our products come from and what do we know about them.
And then certainly the worldwide contamination of the heparin supply profoundly served to underscore the importance of the conversations that were already well underway, especially in the negotiation of product safety agreements.
As a result of a U.S.-China strategic economic dialogue, the FDA and what was then China’s State Food and Drug Administration and its General Administration of Quality Supervision, Inspection and Quarantine agreed to negotiate legally binding product safety agreements as [they relate] to food and medical products. These agreements created a structure (and requirements) for information sharing and collaboration on specific high-risk products. Those very intense negotiations took place quickly, between August and November of 2007, and subsequently led to the decision to establish offices in China, which happened in November 2008. This all happened within a year.
It was rather significant to negotiate legally binding food and medical product safety agreements between the United States and China over a four-month span, with some additional strategic economic dialogues in April and May, which allowed for the memoranda of agreement to be signed in December [2007]. These efforts involved not only the FDA but HHS, the Department of Commerce, and the U.S. Trade Representative. So, it raised the FDA's profile to have colleagues from Commerce, USTR, and HHS working with the agency. That, to me, underscored how very important it was.
And as I led the medical product negotiating team, we emphasized throughout our negotiations that we wanted to develop a stronger infrastructure for collaboration on the medical product side to avoid facing the challenges that the food side of the FDA had faced in responding to the melamine presence in animal food.
But we had some tension about why we needed to do that, because if there wasn't a problem with medical products, why should we negotiate agreements? In the end, the importance of negotiating those agreements on the medical product side became evident in responding to the heparin contamination. We were then able to use the agreements – the commitment to share information – to speak more openly about product safety problems, to investigate and respond to the presence, (or rather the replacement, at some level) of heparin with oversulphated chondroitin sulfate.
The product agreements were very China-specific. But there was also a recognition of the need to address imports, not only from China, but from all over the globe.
We learned in that negotiation process about the importance of engagement and being able to have the conversations with colleague regulators, to be more local, and have awareness of what was happening to regulated industry in those places – whether that might be major weather events that affected crops or transit of active pharmaceutical ingredients, civil unrest that affected supply chains, or changes in local regulatory structure and oversight. This led to the FDA saying we need a larger presence beyond the U.S. border.
What was the thinking that went into deciding where to open the additional foreign offices? What were some factors that came into play?
It was a combination of things. What activity do we see there? And the relative risk, not only the quantity of product, but what part of the manufacturing or processing is being done in a region?
And then there were locality dynamics to consider. Could you have a presence in Central or South America that would allow you to be able to go to other countries, which would make it, in essence, more than a country office, but rather a regional office? Another factor was the maturity of the other regulators. Where were they in their growth cycle? This was all considered with an understanding that where the offices were placed initially would likely adapt as industries changed, as regulatory environments changed. And so those initial offices were placed where the FDA thought would be the most impactful [location] to launch.
Once the China office was established, how quickly did you see the benefits of having staff there on the ground, building those relationships, seeing the realities of those countries? Did you see an impact immediately or did it take time? Did it vary region by region?
The process of just setting up the China office was very helpful in addressing the heparin situation, as well as melamine in dairy containing products. If you were to compare how the agency was able to inspect and investigate the facilities involved in melamine in animal feed versus melamine in dairy containing products, it was very different. And there was some improvement of the melamine itself that was used in the dairy containing products, because it caused less harm than if it had been the cruder form introduced into pet food. But just the process of setting up the offices (and having negotiated the product safety agreements) helped provide a better familiarity with the individuals involved at the regulatory level. There was a better familiarity of understanding local customs and interactions, and so that really began even before the offices were established. And then, having staff on the ground made a remarkable difference in awareness, and in facilitating conversations.
I saw the same situation play out in South America, although I was in the private sector at the time. I could see the opportunities for the local, regulated industry to have conversations with their U.S. counterparts and, vice versa, for our folks to gain a better understanding of the regulatory environment in Brazil. Having the FDA office in South America facilitated those conversations, which then facilitated regulated industry’s compliance with [FDA's] requirements.
How did your experiences in setting up the foreign offices and being here during that transitional time influence your engagement on the evaluation of the FDA’s human foods program?
We made a conscious effort in constructing the independent expert panels that were conducting the evaluation for the FDA's oversight of human foods and parts of the tobacco program [to include] individuals who had some familiarity with that scope of responsibility beyond the United States.
Also, we made sure that the panel included in their discussion the reality that this is not just a U.S. enterprise. It's not something that can be conducted just within the United States but includes international responsibilities, as well.
The work of the foreign offices was important to the expert panel, particularly for food, in understanding the breadth and depth of activity that takes place outside the United States.
Additionally, the expert panel identified the importance of having a clear decision-making process to facilitate making regulatory decisions, and for it to be clear to other regulators who's in charge. Lastly, this all hinged on a culture that supported decision making versus simply deliberation, and this meant addressing the lack of a clear structure of who makes the final call.
So, establishing a more clearly delineated hierarchy for decision making?
Exactly. Our international counterparts think of the FDA as one entity. Which of course it is, but it has many parts. But the expectation is still to hear one decision or stance coming from the FDA. Whenever there's any question about decision making at the FDA, there can be the perception that the agency isn't committed to a position, or that a decision or a directive isn’t “really” a final decision or directive, and that industry doesn’t need to comply. And that's rarely what the agency intends.
Considering your broader aperture on foreign engagements and your understanding of our relationships with our foreign counterparts, how would this realignment assist in streamlining our messaging?
That was certainly an intent of the expert panel. The goal would be to not only have more clarity within the United States, but more clarity for foreign regulators and industry where it's easier to be confused by seemingly competing messages. Having clarity on who is the decision-maker is important.
How was it working on something as big as the evaluation of the FDA’s human foods program now, with all the misinformation that abounds, as opposed to working in 2007-2008 to establish the foreign offices, when misinformation was not so pervasive?
It was different, in both a positive and negative way in that there were fewer ways for everyone to share information. In fact, at one point we were told by our Chinese negotiating partners that if we could just control the U.S. Congress and the U.S. media, we wouldn't have a problem. That simply is not the way our democracy operates. And so that was not going to happen.
However, in 2007-2008 mass communication was largely accomplished through the media. There were some things that were communicated directly to the public, but largely the communication of agency activity or anyone's activity was driven through the media and more traditional media establishments.
You still had a proliferation of misinformation. It was just different in that a misunderstanding of facts or incorrect positions were shared in personal conversation versus on a social media platform that allowed people to influence many, many other people.
On the other hand, these same social media platforms now allow the FDA to reach many, many people directly. This means that while misinformation may spread quickly, the agency can reach more people directly, and in a timelier manner.
I think it's a challenge and an opportunity because it does give the FDA an opportunity to clearly communicate directly. And that allows the agency to think through and better prioritize the science, the policy, and the communication, and make sure that all of that is packaged together, which I think is particularly important in global activity. Sometimes the most important thing about a regulatory decision is who you tell, when you tell them, and how you tell it. Let me give you an example.
I recall there was a phone call on a Saturday night about botulism in some canned product, and we needed to get the word out to have people check the expiration date for those specific products. And thankfully, one of the brilliant communicators who worked at the agency at the time, Dr. David Acheson, he coined a phrase, “Well, you don't want these to explode in your pantry”, and that visual – that message – is what piqued the media’s interest. That helped us because, at the agency, we were struggling with how to reach people to better help them.
This is part of what's improved in communication since then. Today you hear more from retailers about what you've purchased because they have better tracking systems. People now can be informed more directly now, by the FDA and other stakeholders.
But communicating directly to consumers (and not just “talking at” consumers) requires listening to consumers and adapting information and communication to be better understood.
I think the foreign presence helps us with those situations where a phrase or an approach that might be well understood in the United States simply lands flat, or offensively, or falsely, in another culture.
But it's beyond the simple translation. It’s the broader interpretation and communication that help the FDA have a better understanding of just what's happening in each country and why it is important. Also, the foreign offices have the ability to assess how the agency's decisions or communications or activities are being perceived and understood, which can then help to improve our foreign counterpart’s understanding.
Here’s an example from a personal experience. Would you travel to India during the national holiday? Probably not, right? Well, I was in India a few years ago, when it was their equivalent to our Fourth of July, and I assumed everything would be closed. But the India Office staff informed me that everything was, in fact, open. Everyone will just have ceremonies going on. I wouldn't have known that. So, I went and saw the facilities that I was supposed to see, and I observed multiple ceremonies, and it was fascinating. But would I have known that without that firsthand information? I don't think so.
In your opinion, what do you think are the FDA’s biggest challenges and opportunities in the next five years?
That's a great question. Geopolitically, it's a changing environment.
Did we learn in the pandemic that maybe our far-flung supply chains, without sufficient redundancy, are not that great? And are they at risk of nationalist decisions? When faced with a threat, what does any nation do? They aspire to protect themselves.
So, in a changing geopolitical environment where nearshoring or manufacturing redundancy, or some of these other things are increasing in importance, I think it is really important for the foreign offices to convey to other countries that these steps are being taken, not because you failed us or you've done something wrong, but more about an effort to develop some of those things closer to home.
Also, what can we do to strengthen and improve our efforts globally, so that all economies can access vaccines, respirators, cotton swabs?
But I think that's different from 2007, 2008, 2009, and probably for a decade after that, where the goal was to expand and globalize supply chains, with a very focused effort on making things in the least expensive place possible, regardless of how far-flung that might make manufacturing enterprises. Moving product was easy and fast. It’s a different reality today, with a clearer understanding of the disruption caused when borders and businesses are closed.
Also, we've got another explosion of technology and capability with mRNA vaccines and gene therapy, as a couple of examples – that's really an opportunity for regulators globally to say, how can we collaborate? Particularly in gene therapy for rare disease.
What information can we share to help bring these advancements to patients in a number of different countries by collaborating on regulatory efforts or understanding how the regulatory systems fit together?
And there are still some economies and some regulatory environments that may see efforts to move to a global standard as efforts to protect large, multinational companies and to drive out local industry, versus seeing these efforts as truly focused on product quality and to better serve the individuals in that country.
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