Editor's note: On August 31, 2005, Susan F. Wood resigned her positions as assistant commissioner for women's health and director of the Office of Women's Health at the U.S. Food and Drug Administration (FDA). The resignation was in protest of the agency's continued delay on the recommendation of a national advisory panel and its own internal reviewers to approve Plan B-levonorgestrel, commonly known as emergency contraception or the morning-after pill-as an over-the-counter (OTC) product. The drug gained FDA approval for such sale to women over 18 years of age almost a year later, on August 24, 2006. Wood's resignation brought additional public attention to the issue and is credited with finally prompting the FDA to provide Plan B OTC to women 18 and older, more than three years after the initial application.
AJN editor-in-chief Diana Mason recently interviewed Wood, now a research professor at the George Washington University School of Public Health and Health Service, by telephone to discuss why the FDA's approval of Plan B for OTC status took so long.
Diana Mason: What is the process by which a prescription drug attains OTC status?
Susan Wood: The general presumption is that products don't need a prescription unless patients need a "learned intermediary" [a prescriber] to help them determine their particular condition, to explain how to use the product correctly, or to know what product would assist them with their particular concern. But most drugs come in as prescription drugs, so when companies apply for OTC status they are trying to go back to the initial presumption that it does not require a learned intermediary. They have to present data on whether the product label is understandable, so they carry out label-comprehension studies. There are also actual-use studies, which have to do with whether a general population can use the product correctly according to the label, without a prescriber. They should have already demonstrated that the drug is safe and effective.
DM: The company that manufactures Plan B wanted to get OTC status in 2003 and was told that it didn't have enough data demonstrating its safe use as an OTC drug in young women.
SW: Well, that's partly right. It took longer than it should have. The letter that was issued in May 2004 was contrary to the opinion of the professional reviewers within the FDA. It was a denial of OTC status nominally because the company did not have enough women in the younger age groups to do a subpopulation analysis of the label-comprehension and actual-use studies. There were no safety concerns in women in that age group. These products and hormones have been used by girls and women of childbearing age for a very long time. But the issue that was raised was, Did we have enough young women in the label-comprehension and actual-use studies? The opinion that additional such studies were needed was contrary to what the professional staff had recommended and to the general practice of the FDA, which has not required subpopulation analyses in specific age groups.
DM: My understanding is that the advisory committee had little, if any, question about the safety of this drug.
SW: That's correct.
DM: But when the committee took a vote on OTC status for all women, ideology began to seep in.
SW: You could see a little of that in the advisory committee discussion. There were several votes that day; the vote for approval was not unanimous, but it was very strongly in favor of OTC status. Those who objected had a larger issue with making contraception more widely available. But those same people who objected to OTC status also voted that it was safe as an OTC drug. The vote in December 2003 was 23 to 4 in favor of OTC status, and it was unanimous in terms of safety.
DM: At the time you were assistant FDA commissioner for women's health and director of the office of women's health, and as such you didn't have jurisdiction over Plan B, correct?
SW: Yes. I was paying attention because I wanted to make sure everything was done carefully and properly. So I was aware of what was happening but was not part of the decision-making process. The FDA had both the OTC drug division and the reproductive health division working on this application. Normally, if there is agreement, the two office directors involved sign off on the decisions, whether it's an approval or a denial. But in this case they were informed after the advisory committee meeting that they would not be allowed to issue the decision, regardless of whether agreement had been reached.
They were told that some of the issues had to do with the question of risky sexual behavior among young women, in particular. So the reviewers pulled together a lot of studies showing that changing sexual behavior is very difficult, and that easy access to emergency contraception doesn't increase risky sexual behavior. At that point, the director of the Office of New Drugs also strongly recommended approval. However, in May 2004 Dr. Steve Galson, acting director of the FDA's Center for Drug Evaluation and Research, issued the nonapproval letter. The company could come back to the FDA and propose keeping it a prescription drug for those under age 16 and nonprescription for those 16 and older. This decision of professional staff overruled the decisions at every level.
Dr. Galson was prepared to approve Plan B as an OTC drug in January 2005 for women 17 and older--and he apparently was not allowed to issue that decision. Months went by, but at that point no one knew what was going on because no one was being told.
DM: The issue came up in the confirmation hearings of former FDA administrator Dr. Lester D. Crawford in April 2005, Senators Patty Murray [D-WA] and Hillary Clinton [D-NY] demanded that the FDA take some action on Plan B. How did that play out?
SW: Dr. Crawford was confirmed as commissioner with that promise. In August 2005, after being out of the country for several months on a fellowship working with the FDA equivalent in the United Kingdom, I had come back trying to understand what was going on. No one seemed to know, and that was very disconcerting to me. The people who knew the most about the product, the application, and the process did not appear to be involved in whatever decision making was in process. That's quite disturbing, because you really want the people with the most expertise most directly involved in these decisions.
On August 26, 2005, the commissioner made the announcement that, yes, the center was prepared to approve Plan B OTC for women 17 and older, but, no, we were not going to issue that approval because the idea of it being prescription for one group and nonprescription for another was a novel and complex issue. The FDA was going to open it up for the first phase of possible rule making on how to implement this idea. This was a brilliant strategy because the general public doesn't understand rule making and it sounds like just more public comment, which doesn't sound too terrible--it just sounds like a short delay. But to develop a federal regulation takes a very long time, a lot of resources, and a lot of effort, putting the matter in a bureaucratic black hole that would last for years. I was stunned. I knew it was essentially saying "no" without technically saying "no" because they were never going to get an approval out. That's when I resigned. Up to that point, there had been bad decisions made that I disagreed with and I objected to, but there was still some hope that we would get a partially correct decision.
The rule-making process started and opened up for public comment for 60 days. By then, Dr. Crawford had resigned amid allegations of financial improprieties, and Dr. Andrew von Eschenbach came in as acting commissioner; he supported the earlier decisions and the rule-making process that was under way.
When Dr. von Eschenbach came up for confirmation to head the FDA in 2006, Senators Murray and Clinton put a hold on his nomination as they had done with Dr. Crawford. The day before his confirmation hearing, at the end of July 2006, he announced that OTC Plan B could be approved for women 18 and older, and the FDA did not need to go into rule making. Senators Clinton and Murray lifted their hold on his nomination. Plan B was approved for those 18 and older within three weeks. And that was more than three years after the initial application.