The court ruling overturning FDA's restricted distribution of the emergency contraceptive Plan B could have a number of implications for the biopharma industry - ranging from a near-term impact on confirmation of Obama administration nominees to a longer-term curbing of creative product risk management activities.

On March 23, U.S. District Court for the Eastern District of New York Judge Edward R. Korman ordered the agency to rescind its restriction on nonprescription access to Barr Labs' Plan B to women age 18 and older because "no useful purpose would be served by continuing" to require that 17-year-olds have prescriptions for the drug.

FDA's decision to set an age limit and pharmacy-only marketing conditions was "arbitrary and capricious," the judge declared. He also directed FDA to reconsider whether to make the drug available to women of all ages without a prescription.

The ruling cites "repeated and unreasonable delays, pressure emanating from the White House, and the obvious connection between the confirmation process of two FDA commissioners and the timing of the FDA's decisions."

When Plan B was launched, it was Barr's third most important product commercially and the ruling may have little direct commercial impact (¹ 'The Tan Sheet' March 5, 2007, In Brief).

Barr has since been acquired by Teva (² 'The Tan Sheet' Jan. 5, 2009, In Brief).

Stakeholders thus may be tempted to dismiss the whole controversy as just a tempest in a teapot: Further evidence that anything touching on abortion rights is political dynamite, perhaps, but otherwise not relevant. But this may be a case with limited commercial impact but big policy implications.

A Wild-Card For The Hamburg Confirmation

On paper, the ruling dovetails nicely with some themes of the incoming Obama administration, offering another case study for the White House to use to argue that it is committed to science-based public health policy.

It is possible that the new FDA team, led by Commissioner-designate Margaret Hamburg, would have reopened the Plan B decision of its own volition to make that very point.

But the Obama administration probably would rather not have this come up in the context of the confirmation process. And biopharma companies, who stressed the urgency of filling the FDA vacancy during the transition, should be wary of any wrinkle that could delay the confirmation.

Regardless of what the new FDA team actually would have done with Plan B, it now has no choice but to revisit the application - and Hamburg is certain to be asked about it in the confirmation process. As the ruling itself notes, Plan B already helped delay the confirmation of the last two commissioners - Lester Crawford and Andrew von Eschenbach.

Reopening Old Wounds Inside FDA

To critics of the agency's handling of Plan B, Susan Wood is the hero of the story. She is the former FDA official who resigned over the handling of the application (³ Also see "FDAer Resigns Over Plan B; Senators Seek Results Of GAO Investigation" - Pink Sheet, 5 September, 2005., p. 3).

Now on the faculty at George Washington University, Wood has been an outside advisor to the Department of Health and Human Services transition team. So, when she was quoted by the Washington Post pointing out that two of the key figures in the review - Steven Galson and Janet Woodcock - still have jobs, that sounded ominous.

Galson now is acting Surgeon General and is considering various options once a new Surgeon General is appointed.

Woodcock, the head of FDA's Center for Drug Evaluation and Research, is one of the agency officials considered most vital to a functional review process by most in industry.

Woodcock is a career civil servant, and no one seems to think it likely that she would be pushed out because of Plan B or any other reason. Still, after a long career at FDA, no one would be surprised if Woodcock decided this was her last transition.

Top-Side FDA Involvement In Approvals

Much of the ruling focuses on the degree of top-level involvement in the decision on Plan B, in effect defining a direct, hands-on role by the commissioner (actually, three commissioners: Mark McClellan, Crawford and Von Eschenbach) as indicating some form of undue political interference in its own right.

That by itself is a potential concern for industry. In this case, the commissioner's involvement appeared to delay an approval. But what of other cases - such as David Kessler's hands-on role in shepherding some of the earliest HIV therapies through the agency - in effect inventing accelerated approval in the context of a specific application?

More importantly, the ruling also highlights the unusual level of involvement of the center director (Galson) in many aspects of the review. The ruling stops far short of saying the CDER director cannot weigh in on approval decisions, but may suggest that FDA may want to better define when or how the director can get involved.

Sponsors upset by a decision rendered at the top may applaud; others hoping for a chance to head off a negative outcome may find it harder to engage FDA's top management without going through a formal appeals process.

The End Of Behind The Counter?

Plan B's currently approved OTC application dictates availability solely "behind the counter," a development that took FDA a big step closer to the idea of a formal "third-class" of drugs, somewhere between prescription-only and traditional over-the-counter. Politically expedient or not, that made it a precedent-setting approval.

That precedent may be overturned. The court ruling specifically addresses a petition seeking to have Plan B made available over-the-counter without restriction. The ruling does not change Plan B's behind-the-counter status, but directs FDA to re-review the question based on the science (with a strong indication that the judge views the science as supporting unrestricted access).

Coincidentally, the Government Accountability Office released a report on BTC status the same day as the ruling, and GAO seems skeptical about the entire idea (see story, ⁴ Also see "Behind-The-Counter Class Requires Investment, With Payoff Unclear– GAO" - Pink Sheet, 30 March, 2009. ).

Discouraging "Creative" Risk Management

While the court leaves it to FDA's discretion to reconsider the question of behind-the-counter status, the order changes one condition of the approval right away: Plan B is to be relabeled for use by those age 17 and up, rather than the current 18 and up restriction.

That overturns a last-minute change to the proposed label for the OTC version of the drug that the court attributes to former Commissioner von Eschenbach.

He "decided that 18, rather than age 17, is the 'more appropriate cut-off point' for OTC use of Plan B because of 'well-established state and private-sector infrastructures [which] restrict certain products to consumers 18 and older."'

That, in the judge's view, was entirely unsupported by FDA's administrative record.

It may, however, seem logical: 18 is a well-defined milestone defining the boundary between teenager and adult. That rationale may be similar to some of the types of suppositions the agency is starting to make more routinely in negotiating risk management plans with sponsors.

At its heart, the risk management process involves additional controls in the commercial setting intended to align better with real-world practices. The logic of the Plan B ruling suggests that FDA may need more than common sense to justify a restriction on access that isn't supported in the clinical database.

Less Predictability In Advisory Committees

The Plan B ruling highlights the advisory committee process for two reasons. First, the court puts great weight on the fact that the advisory committee reviewing the switch voted overwhelmingly in favor of approval but FDA ended up sending a "not approvable" letter.

The court notes that FDA is not bound by advisory committee rulings, but cites a Government Accountability Office review of Plan B showing that the agency never previously overruled an OTC switch recommendation.

Any sponsor who gets a positive committee review and then a rejection from FDA may think that's good news, but that may not be so. There seems to be little belief among stakeholders that a sponsor would win a case against FDA solely on those grounds. More importantly, if FDA is (or perceives itself to be) bound by advisory committee rulings, the agency will be much more conservative in its approach to those meetings, and less likely to even ask approvability questions if it is concerned about a "wrong" answer.

The ruling also touches on a more current issue about staffing committees, concluding that FDA's leadership tried to stack the committee with people who would vote against the application.

The ruling then notes that CDER officials say that is contrary to standard practice: "CDER is 'not . . . looking for people who have an opinion coming in. That's exactly what we don't want. We want people who can look at what's before them and render an assessment and recommendation on the basis of that." That sentiment now goes by the name "intellectual conflict of interest" (⁵ Also see "Prasugrel Intellectual Bias: FDA Makes Changes, Congress Demands Answers" - Pink Sheet, 9 March, 2009., p. 33).

Chilling Effect On Pre-NDA Commitments

The ruling also could affect FDA's communication about approvability issues in the pre-NDA setting.

The judge cites FDA's pre-new drug application discussions with Barr about its "actual use" study plans for Plan B as evidence that its subsequent concern about use in adolescent girls was a fig leaf for political issues. The ruling stops well short of declaring that the agency's pre-NDA discussions should be treated as binding.

Still, some sponsors may read the case as a reason to rethink the conventional wisdom that suing FDA is a waste of time and money at best, and counterproductive at worst. Food and drug lawyers interviewed agree that there is no reason to change the conventional wisdom. In their view, Plan B is an outlier, a rare circumstance where suing the agency can (and did) work. And, they note, Barr didn't file the suit, women's health advocates did.

However, the ruling could still cause the agency to consider new policies about pre-NDA communications.

That raises at least the potential that advice to sponsors may be less valuable because the agency will be more careful about avoiding any implication that any given data set will justify approval without further review.

- Michael McCaughan (m.mccaughan@elsevier.com)

Plan B Ruling: Little Commercial Impact, Big Policy Implications

More from Archive

More from Pink Sheet