Interview: Janet Woodcock’s lasting influence on FDA

This Wednesday will be Dr. Janet Woodcock’s last day at the US Food and Drug Administration (FDA), capping a remarkable 38-year career at the agency. She’s been called one of the most powerful and influential drug regulators worldwide.

Last Thursday, Focus sat down with Woodcock in her office at FDA’s White Oak campus, where she reflected on her beginnings at the agency: a rather disorienting first day, the mess she inherited at the Center for Drug Evaluation and Research (CDER), and her insistence that CDER be moved away from the Parklawn Building to maintain independence from the commissioner’s office.

She also discussed the crises that arose throughout her career, the importance of a “version 1.0” drug in a therapeutic class, and how she’s dealt with a “cottage industry” of FDA critics – and defended some the agency’s more controversial decisions. One item on her long wish list from Congress: mandatory drug recall authority. She also opened up about what she’d like to be remembered for and her plans for retirement.

Woodcock began her career at FDA as the director of the Division of Biological Investigational New Drugs at the Center for Biologics Evaluation and Research (CBER) in 1986, before taking on several acting director posts within the center, and later being confirmed as the director of the Office of Therapeutics Research and Review in 1993. In 1994, Woodcock took the helm of CDER, a position she occupied for more than half her tenure at the agency. Most recently, she has held multiple roles in the Office of the Commissioner, including as acting commissioner in the first year of the Biden administration, and in her current position as principal deputy commissioner.

This interview has been edited for length and clarity.

Focus: What do you feel are your most significant accomplishments during your career at FDA? You’ve been credited with the development of the modern framework for evaluating drug safety and efficacy, the REMS program, Sentinel, the Critical Path Initiative, and the Pharmaceutical Quality for the 21^st Century initiative. You’ve also been instrumental in promoting new programs for rare diseases and individualized therapies and patient focused drug development.

Woodcock: I think my biggest accomplishment is building organizations that are strong and can persist into the future and continue to grow and evolve, because drug regulations have to be evolving as the science changes so fast. I feel like I left CDER in a good place and I can see the pharmaceutical quality stuff is continuing to move forward and change, and that is what needs to happen. I think introducing and pushing the genomic revolution and how this is affecting medicines has been something that is very important. [Other accomplishments are] legislation pushing for biosimilars, which I testified for, and we got the generic drug user fee program – and with OTC [over-the-counter drugs], I worked with industry to get not only the user fee program but to change how we determine OTC status.

I was very instrumental in getting the 21^st Century Cures Act, which I think has helped the entire agency and got us out of the antique hiring practices that were holding us back.

Focus: You’ve also been a key figure in the reorganization of the Human Foods Program and ORA. What do you think will be the impact of the reorg on industry? It’s been called the largest reorganization in FDA history.

Woodcock: It has to undergo extensive review, and it is not finalized until everyone signs off on it, and we hope that will happen this year. I think that the impact on different industries will be different. Obviously, it will have a profound impact on the food industry and on our partners in the states because it was in response to criticism that drove this reorganization.

We hope to move the centers much closer to the inspectorate. What industry should see is FDA speaking with one voice. We are going to unify compliance functions in the center, so you won’t have this process [where issues] go to the inspectors and then it goes to the compliance staff. If we need a regulatory meeting, all these offices will be involved. Back in the day, there were district offices that were right near their facility. Now we have multinational corporations … we have much better communications and we can all be in the same meeting no matter where we are located.

Focus: On the legislative side, what new authorities would you like to see FDA get from Congress?

Woodcock: Let me say it would be a long list. It is not just about FDA gaining a whole lot of new authorities. There is a lot of clean up that should be done. Many of these statutes were passed 30 or 40 years ago, and often we’re contorting ourselves. How do you fit gene therapy into a statue that was passed in 1980 or 1960?

The legislative process is tumultuous and always has been, so there has always been some reluctance to do that.

Also, FDA does not have mandatory recall authority, that is fine for a big company but for a small company that somehow just slips their product into the country, and they get through somehow by misleading someone at the border and then we say they have to be recalled. They say ‘no.’ What are we going to do? We have to go to court. This is a threat to the public, especially when other countries have mandatory recalls.

Focus: What were some of the most challenging crises you’ve been through at the agency? The contaminated heparin crisis in 2008, or the New England Compounding Center (NECC) meningitis outbreak in 2012 which led to the designation of 503B outsourcing pharmacies?

Woodcock: With Jane Axelrad, we got Congress to found a new industry, which is the 503B compounding industry because there is need and a niche for it. These people who were just ordinary pharmacists who were not cutting it, they did not understand sterile manufacturing and much of the need and the niche for this was in sterile products. Congress founded that new industry and we have been trying to regulate it and that has been a very rocky path, but it is a lot better than having your corner pharmacist making some sterile drugs in volume.

With NECC, I went up and testified in the criminal trials. They were maintaining that they were writing individual prescriptions to Mickey Mouse and to Minnie Mouse … and they said “we don’t do this very often,” that was their defense. They were clearly making large volumes and they were much larger than what we detected. A lot of the people who survived [the tainted drugs] never fully recovered.

There were many other [crises]. When I went back to CDER [in 2007] that is when the rosiglitazone situation happened. The advisory committee said that we don’t think that rosiglitazone is different from any other drugs. You would have thought it was the end of the world. There was Vioxx and there was Celebrex and then the [erythropoietin-stimulating agents] stuff, it went on and on and never stopped. But compared to the past, the drug safety issues are much more under control if you look at it historically. You don’t see every couple of years that drugs are causing huge catastrophes.

Editor’s note: In the 2000s, GlaxoSmithKline’s Avandia (rosiglitazone), Merck’s Vioxx (rofecoxib), Pfizer’s Celebrex (celecoxib), and Amgen’s Epogen/Procrit (epoetin alfa) were the subject of different safety-related inquiries. Avandia was approved in 1999 to treat type II diabetes, yet subsequent reports in 2007 found this medicine could have an adverse impact on patients’ cardiovascular outcomes. GSK eventually plead guilty and paid $3 billion to resolve criminal and civil cases related its promotional practices for several drugs, including Avandia, in what was at the time the largest health care fraud settlement in US history. Both Vioxx and Celebrex were found to increase the risk of heart attacks and strokes, and Merck eventually voluntarily withdrew Vioxx from the market. In the case of synthetic erythropoietin-stimulating agents, like Amgen’s Epogen (epoetin alfa), which was approved to treat anemia in cancer patients, FDA eventually instituted a REMS due to an increased risk of cardiovascular events and the possible progression and recurrence of cancer.

Focus: Can this be partially attributed to REMS and Sentinel?

Woodcock: All of the above. I reformed the drug safety programs and formed the [Office of Surveillance and Epidemiology] long ago. I built the FAERS [FDA Adverse Event Reporting System] system, because when I took over the reporting system, we were using microfiche, and they were 25,000 reports behind. They were in boxes in the next room. I asked them why [reports were in microfiche]. They said, ‘We have to send them to this state and they get tagged and then you send them to another state and they get microfiched and that is our system.’

Focus: You were using microfiche?

Woodcock: That was in 1995 and David Kessler was our commissioner, so I marched in his office and I said you have to give me $3 million and I’ve got to build a system, because with MedWatch we will just put them in more cardboard boxes in this room in the Parklawn Building. I got CDER onto much less paper and made them do [electronic signatures] and electronic records and electronic submissions by 2000, but that was a huge struggle.

By 2000, things were in much better shape. We won a federal IT award for building FAERS and we built DFS [divisions file system] which was the electronic repository. [Before DFS] they would file paper minutes and letters to companies in the document room. The document rooms were miles of linear files, and everything was lost. So, they would not be able to remember what they told a company before. It was awful when I went down there. I told them this has to stop. I told them you cannot approve or not approve a drug anymore unless you do an [electronic signature] and put it on an electronic letter. When I took over the division it was so antiquated … I said I want the budget figures for 1993, and they said, ‘we don’t have a budget.’

Focus: You didn’t have a budget when you took over?

Woodcock: There was no budget. They said ‘we keep a big pot of money." They told Debbie Henderson, who came over with me, ‘Why does she want the budget files?’ and she told them, ‘Well, she is the center director.’ They just kept the money in big pots and doled it out if people asked for it. Had I known, I don’t know whether I would have taken the job on. I told them we are going to have a planning retreat in the summer of 1995 and these division directors looked at me and said, what is planning?’ I will never forget that.

I took over 25,000 reports in boxes, no budget figures, no planning, no real executive staff, and no policy shop. Jane Axelrad was on detail from NRC [Nuclear Regulatory Commission] and she helped [FDA] with the generic drug scandal. I asked her to stay. I needed her help to build a policy shop.

Focus: It sounds like CDER was like the Wild, Wild West.

Woodcock: I really had to build it up. CDER still had older clinicians dictating to secretaries their reviews and they would type them with carbon paper … I just had to breathe. I had to reset the whole system. That’s why this reorganization of ORA and the foods program is not hard because I was down that road before. I was pretty fearless having been through this before.

Focus: Were there many women when you started at FDA?

Woodcock: CBER was more egalitarian because they were research based and so they had women scientists and reviewers. CDER, when I went over, I just faced a sea of men, and a least six of them had applied for the job.

Focus: Did you feel welcome at CDER?

Some people were very gracious, and some people were very grumpy. But I was in the sense that there were so many things wrong, and it was so irresponsible of them not to deal with it that I really had no patience with that.

Focus: Sounds like you had to really speak up and hit the ground running when you first started at CDER.

Carl Peck’s secretary gave me this office, and she said ‘here is your new office.’ I sat in this chair and the desk was bigger than this table and my chin was [lower than the table], and I said the first thing we are going to do is get me a new desk and a new chair. [Editor’s note: Carl Peck was CDER’s former director]. Every time it rained, the water poured on the floor. This was in the old Parklawn building.

My first theory is that we are moving out of the Parklawn building because I felt the commissioner’s office was super disorganized and they had too much influence. When I told Jane Henney [the former FDA commissioner from 1999 to 2001] I wanted to move out, she said ‘no you need to be close to the seat of power.’ I waited. Then she left and we moved out because I had no desire to be close. I had to get things in order and the commissioners then were very reactive to what was going on. We needed a budget and a plan and so forth, I brought Russ Abbott over from CBER and he was very organized and very good, so he helped. I just brought different people in, they did not have a notion of management team, it was all about clinical trial methodology.

Focus: You’ve faced criticism in recent years for some controversial approval decisions, such as the approval of Sarepta Therapeutics’ muscular dystrophy drugs over objections from the review team and Biogen and Eisai’s Alzheimer’s treatment Aduhelm after a negative vote from an advisory committee. There were concerns that the FDA was working too closely with Biogen to get the drug approved. Can you speak to the decision-making process on those approvals and respond to those criticisms?

These things are judgment calls, and literally thousands of drugs have been approved under my purview and most of them have not caused a lot of controversy and most of them have been OK. Not all of them. Sarepta was a judgment call, and I had no issue with people appealing that. That is within their rights. With the Alzheimer’s drugs, it is crystal clear they are effective. You might argue that there are issues of price and difficulties with access, but these are not within FDA’s purview. But as with any dreaded disease, like cancer, we got a lot of criticism about our cancer approvals, yet mortality from cancer has dropped significantly. We’re not going to make progress against Alzheimer’s unless we get to version 1.0, then we can move forward … but I do feel comfortable with all the decisions I’ve made, and you have to let the chips fall where they may.

People have told me ‘you are so decisive,’ and I was never aware of that. I’m just focused on getting things done. I listen and make a decision and move on. I am just not a hand wringer. I love what Steve Galson said, there is a cottage industry in academia of criticizing drug approvals. Editor’s note: Galson was a former director of CDER.

You have to make the best decision you can. It’s easy to be a critic. What I have seen over the years is that you need a version 1.0. If you don’t start with that, you’ll never address that disease if you are insisting on a huge impact on the first try. But look at myeloma and so many of these diseases where we are actually controlling them now, whereas before they used to be death sentence.

A lot of breast cancer patients are living for years, they have stage 4 metastatic breast cancer, and they are still living for years [and] they are living full lives. I think that Rick Pazdur has endured a great deal of criticism for his accelerated approvals and some of them just don’t work out. But our cottage industry out there can’t accept that.

Focus: You’ve also faced criticism over the agency’s handling of the opioid crisis and for continuing to approve highly potent new opioids, such as Zohydro ER, Dsuvia, and Opana ER. What do you think the agency could have done differently, and what can it do to address the opioid crisis going forward.

All opioids are lethal potentially, just like most cancer drugs. We went a long time, we approved MS Contin in the 1980s and there was no problem there because people need morphine. So as far as Opana, that’s like saying ‘we closed the barn door when the horses are way in the lower 40 already.’ My approach to that was we needed to deal with the whole class in some way. We could not ignore the ones that were out there that were causing the problems and tell these manufacturers who were developing these drugs that we are shutting the door and changing our standards because these other drugs are causing the problem. That was my attitude. So, hydrocodone [Zohydro] went off the market, but the roots of the epidemic were in the pain movement and the fact that oxycontin became a cult drug and was pushed out there. That had happened in the late 1990s.

Editor’s note: Opana ER was first approved in 2006 for the management of moderate-to-severe pain. FDA requested its removal in 2017 because of the drug’s potential for abuse.

Focus: Sounds like some things were beyond your control.

Maybe we could have done more. We sent Purdue a warning letter about MS Contin during that time and we sent them warning letters about oxycontin and we forced a label change in 2000 on oxycontin, but the epidemic had many roots and oxycontin prescribing leveled off after that change, but the epidemic really didn’t level off.

Focus: There is now a new office at FDA dealing with opioid addiction.

We did what we could, and perhaps people should say we did more, but to say we caused this, that is an exaggeration. What about the pill mills. Why were they not shut down? They gave states income for years. Everyone knew what was going on. They were shipping thousands and thousands of pills out the door every day. But people look for someone to blame. I understand that.

Focus: Do you have any message to regulatory affairs professionals on how the field is evolving? Do you have any thoughts on the evolution in the field of regulatory science?

I would say to look for opportunities for simplification and streamlining and get behind those efforts. Get behind this ICMRA project on manufacturing supplements for example. I went and talked to many of the manufacturing quality people back in 2000s and I asked them ‘what is your quality objective?’ Some of them would say ‘our objective is to pass the inspection’ and I said ‘that is not a quality objective.’ Don’t be reactive is my motto, figure out what the problems are and try to figure out solutions. Can this be simplified? Is this out of date? This is what I’ve done my whole career is trying to get things modernized and streamlined and use the best technologies and the best approaches.

Editor’s Note: The International Coalition of Medicines Regulatory Authorities (ICMRA) in 2022 announced it was seeking industry participants for two pilot programs, one exploring a common regulatory framework for assessing manufacturing facilities in hybrid inspections and the other for reviewing post approval changes.

Focus: What would you like to be remembered for?

Building organizations that are capable of evolving and changing with the times and having leaders in place who are leading and making these things happen. I should not have had to take over an organization that was dealing with microfiche and carbon paper in 1995.

Focus: Do you plan to stay in the public health field once you leave FDA?

I have other plans. I’m not going to have anything to do with FDA or drug regulation. First of all, I am recused for a full year, like a cooling-off period, and I don’t want to anyway. I have overt plans not to do anything. I’ve been there, I’ve done that. I have another project that I want to start, which I’ll talk about in due course. I have my garden, traveling, my orchids, I have a new grandchild, she’s very cute, and family. I have many things I want to do and can do. And so I’m that kind of person, once I leave, I’m gone!

[Editor's note: This article was updated on 29 January to correct a reference to an individual.]

Interview: Janet Woodcock’s lasting influence on FDA

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