Deals Of The Week's Takeaway From PSA: Optimism With Aches

The federal government may be on the verge of a shutdown, with ‘unprecedented implications’ for new drug reviews, as our friends at Prevision Policy in D.C. put it in a note on Sept. 27. But in New York, the overall mood among investors and industry stakeholders attending Elsevier Business Intelligence’s 23rd annual PSA: The Pharmaceutical Strategy Conference last week was uncharacteristically and surprisingly upbeat.

Surprisingly, because anyone who has been involved with pharma for even a little a while has heard investors of all stripes rail against FDA, EMA and regulatory agencies in general as a chief contributor to industry’s malaise. Yet, industry experts at PSA were gushy about both FDA and the general state of R&D creativity.

Pharma’s R&D woes are well known – but they are on the scale of “fevers and chills and aches,” said McKinsey director Ajay Dhankhar, who opened the meeting on Sept. 24 with a talk on the “new math of innovation” – not death rattles.

Better than breaking down the R&D model and starting over at the core, as some have claimed necessary, he suggested that the industry needs to engage in “punctuated evolution” – in which it experiments in a few areas and takes big leaps. In other words, he argued, minor improvements in multiple areas could add up to big enough swings in productivity, which can put industry on solid footing and allow for the kind of leaps forward that result in longer-term, larger improvements in growth.

The IPO bull market obviously colors perceptions, but some of the leading institutional investors, empaneled to discuss investor perceptions on Sept. 24, even had praise for the much-maligned FDA and in particular agency commissioner Janet Woodcock. The quality of communication between FDA and companies has improved significantly, noted RA Capital’s Rajeev Shah, with the agency becoming more predictable, a change that is critical to investors. Speaking of the bull market, investors agreed fundamentals remain strong. The key market catalysts to watch, they said, are the performances of the “big four” biotechs: Biogen Idec, Amgen, Gilead Sciences., and Celgene.

At the other end of the investor spectrum, venture capitalists are also optimistic, a tone that VC panelists conveyed at PSA and one that is supported by more substantial quantitative, albeit nuanced, data compiled by our sister publication START-UP in its September 2013 issue.

Even opportunities in fraud-investigation-rattled China came in for kind words, despite the wave of publicity about big pharma’s compliance problems there. Heads of three Chinese companies that have commercial deals with Western pharma to sell innovative drugs in China argued that market remains a great growth story, with plenty of opportunity, in light of the ongoing health reform initiatives there.  Compliance woes for some are good news for others, and while “at the moment there is a lot of focus on this, fundamentally, it will not change the attractive situation in China for the pharma industry,” said Friedhelm Blobel, CEO of SciClone Inc., a U.S.-Chinese hybrid company that partners with Western companies seeking to sell their drugs in China. For those interested in more on China, attend Elsevier's upcoming PharmAsia Shanghai Summit in October.

About 250 attended the meeting and for those who weren't there, read about it in "The Pink Sheet" and twitter, under hashtag #PSA13. Meanwhile, as PSA strove to gain a sense of trends shaping deals to come, here are a selection of this week's deals that have happened: --Wendy Diller. (Note of thanks to Takeda for photo of Tachi Yamada speaking at PSA 2013)

AbbVie/Galapagos: AbbVie had a busy week, announcing its second drug-development collaboration in as many days on Sept. 24. The new deal is an alliance to develop cystic fibrosis therapies with Galapagos, marking the second tie-up between the companies in two years. The deal  extends from discovery through registration, with a goal of improving upon competitor Vertex's nascent success in addressing the root causes of the disease with small-molecule drugs. Vertex has investigated compounds that mediate mutations in the cystic fibrosis transmembrane regulator (CFTR) protein. That company made a big splash with CFTR potentiator Kalydeco (ivacaftor), a channel-opening drug that addresses the G551D mutation in CF patients, when it obtained FDA and EU approval last year.

The goal of the AbbVie/Galapagos collaboration is to develop both CFTR potentiators and correctors, moving a potentiator molecule into Phase I by the end of 2014. Galapagos will be in charge of discovery and Phase I and II development, with R&D input from AbbVie. The North Chicago, Ill.-based pharma currently markets CF drug Creon (pancrelipase), which yielded U.S. sales of $196 million over the first six months of 2013, up nearly 26% from its 2012 pace. AbbVie’s previous deal with Galapagos is part of its search for a pipeline replacement for top seller Humira (adalimumab), which loses patent protection in 2016. In 2012, it paid $150 million up front for Galapagos’ selective JAK1 inhibitor GLPG0634 for RA. - Joseph Haas

Ablynx/Merck Serono/AbbVie: Drug-discovery company Ablynx had a good week, unveiling two R&D alliances with key big pharma clients that could lead to novel Nanobody pipeline assets. On Sept. 23, the Belgian biotech unveiled a global license pact with AbbVie to develop and commercialize the anti-IL-6R Nanobody ALX-0061 to treat inflammatory diseases.

Two days later, Ablynx and Merck Serono announced a multi-year research alliance that could lead to at least four co-discovery and co-development collaborations and bind the Belgium-based Nanobody specialist closer to the German drug maker. Under their latest pact the biopharma division of Germany’s family-controlled Merck KGAA will fund a discovery group at Ablynx numbering up to 30 people, and the two will select disease targets jointly. The team will seek to identify Nanobodies to tackle these during a four-year alliance. Merck Serono will provide €25 million ($33.8 million) in funding over the first four years, including an initial payment of €11.5 million, with an option to extend the alliance a further two-and-a-half years if it’s successful. The Nanobodies R&D pact is that duo’s fourth.

The first, signed in 2008, focused on two targets in oncology and immunology, and was followed by a second in 2010 that added a new program for an inflammatory diseases target. In November 2011, they entered a third agreement to co-discover and co-develop Nanobodies against two targets in osteoarthritis. The R&D collaboration will span all of Merck Serono’s core R&D fields, including oncology, immuno-oncology, immunology and neurology. It will aim to deliver at least six programs with proof-of-principle in a relevant animal model. If there is sufficient in vivo proof-of-principle generated by the programs, Merck Serono will commit to taking at least four programs forward with Ablynx in co-discovery and co-development arrangements. If all goes to plan, the pact will run six-and-a-half years and generate cash in-flow of up to €100 million for the Belgian Nanobody specialist. Under its deal with AbbVie, Ablynx will receive an upfront payment of $175 million, which will be earmarked for clinical development of ALX-0061. If the candidate reaches certain development, regulatory, commercial and sales-based milestones, Ablynx is eligible for $665 million in additional milestone payments, along with double-digit tiered royalties on eventual net sales. - Sten Stovall

Servier/Egis: Being the first company in Europe to bring a biosimilar monoclonal antibody – infliximab – to the market could very well have provided the spark to bring to an end the 18-year arm's-length relationship between the Hungarian generics company Egis Pharmaceuticals and its majority shareholder, the private French company Servier.

Servier has offered 28,000 Hungarian forints, or around $125, a share for the 49% of Hungary’s Egis that it does not own, the privately owned French company announced Sept. 24. Egis no longer needs a listing on the Budapest Stock Exchange to raise funds, Servier said, suggesting the buyout was a tidying-up exercise. But with Egis’ sales revenues currently rather flat because of regulatory and reimbursement changes in Hungary and other countries in Central and Eastern Europe, and a growing appreciation of the future sales potential of the biosimilar infliximab product, Servier’s move appears well-timed.

Egis entered into an agreement in 2010 with South Korean company Celltrion to market its biosimilar infliximab as Remsima in Central and Eastern Europe, and as Flammegis in the Commonwealth of Independent States (CIS), countries such as Azerbaijan and Belarus. The European Commission approved Remsima, and the same product from Celltrion’s Western Europe licensee, Hospira, on Sept. 10. Servier’s offer is valued at $483 million, and is set to close over the coming months. The company noted that the offer, which was at a 33% premium over the previous day’s share price, was generous and would not be revised or updated. - John Davis

Allergan/Medy-Tox: The maker of Botox is defending its position as the market leader in the neuro modulator space with a global licensing deal – excluding Korea – with Korean pharmaceutical company Medy-Tox. Allergan agreed to pay $65 million upfront, $116.5 million in potential development milestone payments and $180.5 million in commercial milestones, as well as royalty payments for the right to develop and commercialize neurotoxin product candidates, including a liquid injectable.

The deal fits into Allergan’s sweet spot since Botox is its biggest drug; the product, which until recently derived most of its sales from cosmetic applications as a wrinkle reducer, brought in $970.9 million in the first half of 2013. The company has said that Botox has taken a 77% share of the neuro modulator market, which grew by 13% in 2012. Currently, Botox has eight indications that include migraines, overactive bladder and excessive sweating. Yet, Botox is a dry powder that physicians need to reconstitute – the liquid injectable could offer a more convenient alternative for some docs. Medy-Tox, founded in 2000, is the maker of a Botox-like product dubbed Neuronox that has been on the Korean market since 2006, and has next-generation botulinum toxin products in its portfolio. The company has plans to enter Western markets in 2014 with the ambition of becoming a leader in the botulinum toxin market. - Lisa LaMotta

Novo Nordisk/Adimab: For the third time this year Adimab has non-exclusively licensed its antibody discovery platform to a large biopharma, adding Novo Nordisk to previously announced tech-transfer partners GlaxoSmithKline and Biogen Idec. As with those previous deals, the financial specifics were not disclosed, but Adimab gets an upfront fee, annual licensing payments, R&D milestone payments and royalties on any products developed using its technology. Adimab’s business development plan involved first signing tightly circumscribed deals with drug developers whereby it would quickly provide its partner with monoclonal antibodies (and eventually bispecifics, antibody-drug conjugates and antibody mixtures as it added to its technology arsenal) against one or two specific targets. Novo Nordisk, for example, struck a deal two years ago to sample the Adimab platform around two undisclosed targets. That, and upwards of a dozen other early deals, were designed as demonstration projects, and Adimab’s goal for years has been to whet partners appetites for its technology, eventually earning big paydays by convincing companies like Novo Nordisk to internalize the discovery platform. The small, Lebanon, N.H.-based biotech said it would become sustainably profitable this year based on payments from its first two tech transfer deals, with GSK and Biogen, announced simultaneously in July. This year, the company plans to pay its venture investors their first dividend – a rare feat for a privately owned, discovery-focused biotech. - Chris Morrison

CRT Pioneer Fund/Bacit/Sareum: A co-funding pact to develop a novel class of cancer drugs called CHK1 inhibitors was announced in Britain this week by Cancer Research Technology Pioneer Fund and London-listed BACIT Limited and oncology drug discovery specialists Sareum Holdings. CHK1 inhibitors control a cancer cell’s response to DNA damage. Blocking CHK1 could boost the efficacy of chemotherapy drugs by blocking repair of the DNA damage caused by these drugs, but without harming healthy cells.

It’s hoped the candidate CHK1 inhibitor potentially could treat a range of cancers including pancreatic, bowel and non-small cell lung cancer in combination with DNA-damaging chemotherapy drugs and radiotherapy. The inhibitor also potentially could treat certain neuroblastoma and acute myeloid leukemia types when dosed alone. The candidate inhibitor originates from research in the Cancer Research UK Cancer Therapeutics Unit at London’s Institute of Cancer Research (ICR) by scientists funded by Cancer Research UK – the world’s largest charity - working alongside Sareum researchers and in collaboration with Cancer Research Technology (CRT), which is the commercial arm of Cancer Research UK.

Much of the further work funded by the new investment, announced Sept. 24, will be carried out at The Institute of Cancer Research. The drug candidate is expected to be taken into clinical development at The Royal Marsden NHS Foundation Trust. Rights to the preclinical program have been licensed into Cancer Research Technology Pioneer Fund from CRT and the ICR. Under the terms of the deal, CPF obtains worldwide rights to the preclinical CHK1 inhibitor program and is responsible, for future development and commercialization, funded by CPF, BACIT and Sareum. CRT and the originating research partners, Sareum and the ICR, are entitled to an upfront fee plus success milestone and royalty payments. Financial terms of the license are not disclosed.  As part of the agreement Sareum said it expects to commit up to £800,000 ($1.3 million) to the program in its current financial year. The partners say the overall funding will enable the project to move quickly towards, and potentially into Phase I clinical trials, and the successful outcome should allow for the further development and commercialization of a novel and broadly applicable cancer treatment.

The CRT Pioneer Fund is a £50 million ($80.4 million) fund that has been established with Cancer Research Technology and the European Investment Fund to bridge the investment gap between cancer drug discovery and early development. BACIT Limited is a self-managed, closed-ended investment company listed on the London Stock Exchange. Sareum, headquartered in Cambridge U.K., produces targeted small-molecule therapeutics, focusing on cancer and auto-immune disease. - S.S.

HbA1c Smackdown: FDA’s Woodcock, UK’s Breckenridge Go Toe-To-Toe Over Diabetes Drug Approval Standards

Just when you think everything that can be said about Avandia has been said, along comes an impromptu, verbal sparring match between high-level officials of the U.S. and UK drug regulatory agencies over the role and value of hemoglobin A1c reduction in diabetes drug approval.

In one corner: Sir Alasdair Breckenridge, chairman of the UK’s Medicines and Healthcare products Regulatory Agency, better known as the MHRA.

And in the other corner: FDA Center for Drug Evaluation and Research Director Janet Woodcock.

The setting: the Third Annual Risk Management and Drug Safety Summit in Washington, D.C. on Oct. 18.

Woodcock, who was the first presenter at the meeting, spoke about CDER’s efforts to improve risk management and drug safety since passage of the FDA Amendments Act. She was followed at the podium by Breckenridge, who presented the European perspective on risk management and a pharmacovigilance “tool kit” for assessing and mitigating drug risks.

Near the end of his presentation, Breckenridge turned to the recent regulatory decisions on Avandia, GlaxoSmithKline’s beleaguered thiazolidinedione. Even though FDA and the European Medicines Agency took different regulatory paths – with FDA restricting distribution under a Risk Evaluation and Mitigation Strategy, and EMA suspending rosiglitazone’s license – Breckenridge stressed the extensive collaboration between the two agencies that culminated in simultaneous announcements on Sept. 23.

“If you think about the difference between what Europe has done and what the U.S. has done, in fact I would suggest there was very little difference indeed, and it was an example of regulatory authorities working together in a global manner,” he said. ("The Pink Sheet" offers an analysis of why they diverged in their final judgment.)

Following these glowing remarks about alignment among regulators on both sides of the Atlantic, Breckenridge took the Avandia post-mortem a step further, and perhaps one too far for Woodcock.

“The question I’ve asked myself is if Avandia came through for licensing today, with the information we had, what should be done, what would we have done? How has regulation advanced? Well firstly, it wouldn’t have been approved for efficacy on a surrogate marker [HbA1c]. That would not be accepted,” he said. Some in industry concur that there is now a higher hurdle, at least commercially, for diabetes products.

Fortunately for the audience, Woodcock hung around after her presentation to hear Breckenridge’s speech, and during a question and answer session, while still sitting in the audience, Woodcock pounced on the British knight’s skepticism toward HbA1c. Here is an abbreviated transcript of the exchange, along with some first-hand, editorial observations noted in brackets:

Woodcock: “If you’re not going to use hemoglobin A1c or serum glucose … what are you going to use for efficacy in diabetes? No drug in type 2 diabetes has ever been shown to improve cardiovascular outcomes.”

Breckenridge: “I believe this illustrates the problem with antidiabetic drugs. I believe it’s going to be increasingly difficult to develop any drug for diabetes which has got a suggestion that Avandia did have, and I think drugs like Avandia are going to die at a much earlier stage and be killed at a much earlier stage than developed.”

Woodcock: “I would say the question with rosiglitazone is a safety issue, it’s not an efficacy issue … I think hemoglobin A1c is more than a surrogate … I date as an internist from the era when people walked around with untreated type 2 diabetes. They hit my emergency room they were in hyperosmolar coma. That’s a life-threatening disease. Or they had severe invasive soft tissue infection with gram negative organisms, or they were dehydrated and had blurry vision and CNS issues.”

Breckenridge: [apparently attempting to explain that not all type 2 diabetics are in such dire straits] “I can remember as well, and I’m not sort of swapping stories with you, but patients with type 2 diabetes are the rather large ladies who you see walking around in the United Kingdom and I’m afraid Washington as well.” [disapproving murmurs from the audience]

Woodcock: “But if you go untreated long enough with type 2 diabetes that’s what you get into. It’s a progressive disease. So the idea that you don’t need treatments for type 2 diabetes I think is an incorrect …. ”

Breckenridge: “I’m not suggesting that ….”

Woodcock: “You will get renal failure, you’ll get amputation … It’s a symptomatic disease. People have studied this and they’ve looked at central nervous system effects of hyperglycemia … There are people walking around with blood sugar 300, 400 and so on. That is not good for you, acutely. And sub-acutely, glycemic control has been shown to be correlated with progression of retinopathy, renal failure and so forth, and neuropathy to some extent. [By now standing, holding the microphone and looking as comfortable as a talk show host on a TV production set] So I would take issue with the fact that hemoglobin A1c is a bad surrogate. I think it’s a very good surrogate for efficacy. I don’t think it tells you anything about safety of a drug just like most surrogates for efficacy.”

Breckendridge: “I’m afraid I disagree with you there, Janet. I think by the definition of a surrogate, hemoglobin A1c fulfills all the criteria … and the point I was trying to make was that if you take, in the development of a drug in the latter phase of the drug, and you had a drug which was effective by affecting the surrogate, but it had some other not just potential but huge changes, big changes which were known at the time in a possible adverse event which diabetics are already prone to, the manufacturers, I would suggest, would have a very, very careful look at that before continuing with its development.”

Woodcock: “I don’t think we’re in disagreement, I’m simply saying I thought the earlier definitions [of a surrogate] were mainly done by statisticians, like Prentiss and others … that it should contain all outcomes. That’s completely naive from a biological perspective, because you may perfectly control the disease and kill people from something else. It’s unrelated to the pathway of the disease. So I think expectation that a surrogate for efficacy would take care of your safety evaluation is unrealistic, and I think we’re saying the same thing, which is for chronic diseases there’s going to have to be a much more thorough safety evaluation, it’s longer term, includes more patients, looks for more outcomes than we have traditionally had.”

Breckenridge: “And I think diabetes is an especially difficult case for the reason I described. If you’ve got a disease whose natural history is to develop vascular disease anyway, then a drug which is going to influence that in any kind of adverse way is not good news.”

Woodcock: “The sulfonylureas have long had a warning in the United States for cardiovascular disease because the only time that was studied long-term there was a signal.”

Breckenridge: “And so do the thiazide diuretics, too.”

Woodcock: [laughing] “So there’s a lot of things we don’t know.”

During a break in the meeting later in the day, Breckenridge was overheard describing Woodcock as “feisty.”

Feisty? Perhaps. But definitely defensive of the view strongly held within CDER’s Office of New Drugs that HbA1C reduction, not cardiovascular benefit, is an appropriate efficacy endpoint for new antidiabetics. Woodcok's eagerness to enter the ring on the issue is especially interesting given that outcomes data is now essentially required to demonstrate the safety of the products.

– Sue SutterPhoto "Natalya" by flickr user Snerkie used under Creative Commons License.

Gupta in for Galson: What's Next for Former FDAer?

Anyone looking at the FDA public calendar this week (who doesn’t love to keep track of the comings and goings of government officials?) may have noticed something peculiar: Steven Galson, the former director of the Center for Drugs, was listed as an FDA participant in a recent meeting at the agency.

According to FDA’s website, Galson joined FDA commissioner Andrew von Eschenbach and Center for Drug Evaluation & Research director Janet Woodcock at a “meet and greet” with the University of Florida officials at FDA’s Silver Spring headquarters on December 17. Galson and Woodcock are listed as “other FDA participants.”

There are a lot of changes expected in FDA leadership in the next few weeks, but Steve Galson’s return to the agency was not one of them. So naturally, we were a bit curious. Could Galson, who left CDER in October 2007 to become acting US Surgeon General, be returning to FDA? Or did the agency’s webmaster err in including him on the calendar?

We reached out to Galson to ask him to explain. It turns out he was invited to participate in the closure of an agreement between FDA and the University of Florida on a new fellowship program. That program, which is designed to bring fresh blood into FDA, is a pet project of von Eschenbach’s and one that his principle deputy commissioner, Frank Torti, has been overseeing since joining FDA last summer.

Galson was invited not in his capacity of a former FDA official (despite what the public calendar says), but because the Florida deal involves officers in the Public Health Service, and as acting Surgeon General, Galson is the Commander of the Commissioned Corps. (He’s also a Rear Admiral.)

But that doesn’t necessarily mean that a return to FDA isn’t in the cards. Galson is expecting to be out of a job in the next few months: according to the Washington Post, President-elect Barack Obama has offered the Surgeon General position to prominent neurosurgeon and television talking head Sanjay Gupta.

Galson is a career government official—not a presidential appointee—so he's not expected to be immediately asked leave the Surgeon General’s office once Obama takes office. But with Gupta as the apparent pick as his successor, it looks like Galson will be looking for another job in the next few months. So what’s next for the former FDA official?

Galson says “is not ruling out any possibilities”—including a potential return to FDA. His next move, Galson says, will depend on how certain appointments come out (presumably the FDA commissioner spot), but he's “looking at all options.”

We’re sure Galson has lots of options—in addition to FDA, he has held senior-level positions at the Environmental Protection Agency (as head of the Office of Science Coordination & Policy) and Department of Energy (as chief medical officer) and worked earlier in his career at the Center for Disease Control and Prevention.

But Galson did join FDA specifically to help the agency revamp its postmarketing surveillance program. That was in 2001, and the agency is still revamping its postmarketing surveillance program. We're just speculating here, but maybe that “meet and greet” at FDA will be the start of Galson's next career move.

The Long Campaign for FDA Commissioner (Part 2)

Yesterday, we told you about Steve Nissen's presentation during the FDA/CMS Summit for Biopharma Executives.

He wasn't the only speaker at the conference whose name has been mentioned as possible commissioner material. The opening keynote, for instance, was by Janet Woodcock, the head of the Center for Drug Evaluation & Research and the hands-down first choice of biopharma executives to be the next commissioner.

That is the first reason why she almost certainly won't get the job. As we wrote previously, industry support is definitely not something the Obama team is likely to weigh too highly when it gets around to making the pick. Nor is it likely that the new administration will pass up the opportunity to give the plum post to an outsider it would like to reward, rather than to a career FDAer, even one as abundantly qualified as Woodcock.

Indeed, the day before Woodcock spoke at the Summit, Rep. Bart Stupak (the chair of one of the Congressional committees that oversees FDA) wrote to the President-elect to declare that no agency insiders should be considered for the post even on an interim basis. Stupak, as "The Pink Sheet" reports, wants "a complete change in FDA's leadership."

Stupak, as it happens, chose the losing side in an internal Democratic party fight over leadership of the Energy & Commerce Committee, so his opinion may not carry as much weight as it once would have. But we're betting that the transition team won't be looking to antagonize Stupak unduly by nominating Woodcock for the job.

As for giving her the post on an interim basis, not only would that antagonize Stupak, but it would probably do exactly the opposite of what her supporters want: if Woodcock is the acting commissioner, she would almost certainly leave the agency once a Senate confirmed commissioner comes on board.

So who will the next FDA commissioner be?

We're betting that the closing speaker at the Summit, FDA deputy commissioner Frank Torti, will end up claiming that title--albeit only on an acting or interim basis. That, at least, is what the natural order of things would dictate, a fact that has been clear since Torti joined the agency six months ago.

And after that? Well, that's what campaigns are for.

Stay tuned: On Monday we'll bring you Part 3 of our campaign-for-commish series.

FDA's Internal Advisory Committee Meetings

Avandia. Vioxx. Ketek. Elidel. Palladone.

What do those drugs have in common? The obvious answer is that they are all associated with a major safety problem that resulted in a significant FDA regulatory action—either a “black box” warning in product labeling, or, in the case of Palladone and Vioxx, outright removal from the market.

But they have something else in common as well. In the months preceding those major regulatory steps, each product was the subject of a relatively unknown internal meeting at the Food & Drug Administration: a regulatory briefing.

Regulatory briefings can be described as “internal advisory committees” at FDA—a chance for review divisions to ask others in CDER for advice on how to handle a tricky regulatory or scientific decision. (For more on regulatory briefings, check out our coverage in The RPM Report. If you’re not a subscriber, you can sign up for a free trial to view the article.)

If you’ve never heard of a regulatory briefing, you’re not alone. Regulatory briefings have been kicking around FDA’s Center for Drug Evaluation & Research for more than a decade, but because they are closed to industry—and review divisions don’t always inform sponsors when one is held—many companies are unaware that they exist. But now FDA is holding more of them, as many as one per week. And they are quite popular with reviewers.

The good news for drug sponsors is that regulatory briefings are not intended to be decisional meetings; the final approvability decision remains with the review division after the meeting is over. But given the typical attendance list—John Jenkins, Janet Woodcock, Bob Temple, Doug Throckmorton and 50-100 other drug reviewers—it would be hard to ignore any advice.

A drug does not have to rise to the level of an Avandia or a Vioxx to be discussed during a regulatory briefing—given the frequency of such meetings, that could not possibly be the case. But, as the list above indicates, they do tend to skew toward the more problematic end of the continuum. The need for a regulatory briefings should not spell doom and gloom for a sponsor, but it could be an indication that something is wrong. That alone makes them worth watching.

image via FDA

Transitioning to a New FDA: What's Next for Von Eschenbach?

As Barack Obama said at his first press conference as President-elect on Friday, there can only be one president at a time. Likewise, there can only be one FDA commissioner at a time.

While there’s been a lot of speculation about who might take the reins from Andrew von Eschenbach (see our picks here and here), there hasn’t been a lot of talk about the plans of the current commissioner. When will he leave? Where is he headed? Who will fill in for him until a permanent replacement can be found?

Von Eschenbach himself has remained mum on his post-FDA plans, but we’ve heard that a deanship is in the works—potentially a return to the University of Texas MD Anderson Cancer Center in Houston, where he served as VP and chief academic before being named director of the National Cancer Institute in December 2000.

One thing appears clear: von Eschenbach will tender his resignation before Obama takes office, probably sometime in December, and will leave the agency soon after January 20. That is the typical protocol for presidential appointees--or at least for those not named David Kessler (the one FDA commissioner holdover since the 1950s). FDA officials have been preparing for the transition to a new Administration for months.

Given that the selection of an FDA commissioner is pretty far down Obama’s to-do list, von Eschenbach’s departure will involve a temporary replacement for at least the near-term. Recall that during the last transition after President Bush took office in 2001, it took until early 2002 before Lester Crawford was named acting commissioner, and until November before Mark McClellan was sworn in.

So whomever is named acting commissioner when von Eschenbach leaves could remain in that position for some time. As much as the pharmaceutical industry would like that temporary head to be Center for Drug Evaluation & Research director Janet Woodcock, FDA chief scientist Frank Torti is a more likely pick.

But despite what you may have heard, FDA says von Eschenbach's departure is not imminent. We asked the commissioner’s office about reports that von Eschenbach is packing his bags, and here’s what a spokesperson had to say:

“The FDA Commissioner serves at the pleasure of the President. As protocol dictates, all senior political appointees submit their resignation to the President who appointed them at the conclusion of the Presidential term.

Commissioner von Eschenbach will remain deeply engaged and sharply focused on leading the Agency in accomplishing its mission of protecting and promoting the health of the American people every single day of his service, until the very last day, whenever that may be.”

It Doesn’t Always Pay to Work at FDA

When FDA commissioner Andrew von Eschenbach testified during his confirmation hearing in front of the Senate Health Committee in 2006, he pointed to one area on which he would be dedicating plenty of attention: employee morale.

“Attention to our workforce is my number one priority. It is the most precious asset that FDA has,” von Eschenbach told Sen. Barbara Mikulski (D-Md.) during the hearing. “Improving and enhancing retention and recruitment opportunities, career development opportunities will also address morale.”

Turns out one detail may have been overlooked. Someone forgot to, um, pay everyone on time.

So, at least, says Senator Chuck Grassley. He claims that FDA has some serious issues with its payroll system. Some employees aren’t getting paid, while other are being overpaid by thousands of dollars. That kind of “sloppy record keeping,” Grassley says, has “shaken confidence in the personnel management system.”

“I am very concerned that payroll problems are adversely affecting employee morale and work performance at the FDA,” Grassley says in an October 28 letter to von Eschenbach and HHS secretary Michael Leavitt. One FDA employee, he says, went to the emergency room in the middle of the night with a sick child, only to discover that FDA had incorrectly terminated him, thus cancelling his health insurance benefits.

“On at least two occasions employees may have been mistakenly overpaid by several thousand dollars,” while in another case, “a brand new employee at the FDA was not paid for several pay periods because the employee ‘fell out of the system,’” the letter says. Grassley is requesting that FDA submit all wage- or benefit-related complaints filed since January 2006.

This isn’t the first time that FDA pay practices have attracted congressional attention. House Energy & Commerce Committee Chairman John Dingell and Oversight and Investigations Subcommittee Chairman Bart Stupak have both complained about FDA awarding excessive bonuses to its highest paid employees, while not making a greater effort to retain employees with a scientific function in the agency.

And low morale has been a persistent problem at FDA. An understaffed agency that is always under a threat of whistleblower actions and intense scrutiny from Congress over issues like drug safety doesn’t always make for a pleasant place to work. And unhappy FDA employees aren’t good for drug sponsors—especially if disgruntled reviewers leave before an NDA is approved.

Indeed, Mikulski’s line of questioning for von Eschenbach in 2006 was prompted by a survey released a month before by the Union of Concerned Scientists that found low morale among many FDA employees due to a perceived lack of support from top agency officials.

Even before his confirmation hearing, von Eschenbach talked about his commitment to turn “FDA into an efficient, modern, performance-based organization” with an emphasis on improving “business” operations. And he later named the agency’s first-ever chief operating officer, John Dyer, to focus on “strengthening the management, business processes, and information technology of the agency.”

But as Janet Woodcock, the director of the Center for Drug Evaluation & Research, put it earlier this year, all FDA employees really want are the basics: an opportunity for professional development, good communication from the top, and—believe it or not—decent parking.

Of course, getting paid would be a plus, too.

Balancing Drug Safety and Drug Approvals

Well, it’s official.

FDA’s drug review and drug safety offices have set aside their differences and hammered out an agreement that more equally divides regulatory authorities on issues related to drug safety.

This is a significant change in drug safety policy at FDA: the Office of Surveillance & Epidemiology—seen by some drug sponsors as not quite as friendly to industry as the Office of New Drugs—will now have a greater voice on regulatory issues related to drug safety. In the past, OSE had served in more of a consulting role to OND.

This brave new world was pushed by Center for Drug Evaluation & Research director Janet Woodcock as part of the “Safety First” initiative in response to some very public disagreements between FDA officials on drug safety issues. (You can read more about that in an interview with Woodcock that appeared in The RPM Report.)

While we wrote about the plan to redraw the lines of authority in a previous post, we just got our hands on the memorandum of agreement that makes the deal final. The MoA—between Office of New Drugs director John Jenkins and Office of Surveillance & Epidemiology director Gerald Dal Pan—took effect June 30 and was announced to FDA employees by Woodcock on July 1.

Under the agreement, the drug review and drug safety offices will share equal responsibility on “significant safety issues” for pending and approved products.

Examples include:

1) Safety labeling changes;
2) Submitting and implementing a REMS;
3) Requiring a post-marketing study or clinical trial;
4) Discontinuing marketing of a product;
5) Implementing an educational plan; and
6) Modifying promotion or advertising

Any disputes would be referred to Woodcock; both Dal Pan and Jenkins expect most issues will be resolved without involving the CDER director. Speaking during a town hall meeting at the Drug Information Association annual conference last week, Dal Pan said it will be a “very rare occurrence” to go to Woodcock—or even the office directors themselves—to resolve a difference of opinion. Most disputes will be handled by the office staff, he said.

Under an even bigger change, OSE will be designated as the lead office for certain regulatory actions regarding drug safety:

1) Observational epidemiological studies; and
2) Medication error prevention, including the proprietary name review process

Perhaps even more importantly, OSE will eventually add additional authorities as it staffs up its office and builds its organizational capacity, including pharmacovigilance activities, risk management plans, and the review of carton and container labeling and packaging.

While authority over regulatory actions associated with approvals will continue to reside at OND, responsibility for certain approvals of supplemental applications will eventually be transferred to OSE, the agreement says.

Woodcock said she sees the agreement as “just the first major step” toward creating a new culture at CDER—one that “supports the work of multidisciplinary teams, provides an environment where each member of the team has an opportunity to express his or her view, and ensures an avenue for promptly raising unresolved differences of opinion through the management chain for prompt resolution.”

image from flickr user billogs used under a creative commons license.

CDER Hiring Frenzy: More Reviewers Means Faster Reviews

Anyone concerned about today’s troubled economy and their own future employment prospects should submit a job application to FDA’s Office of New Drugs. They’re hiring.

Indeed, OND is on a virtual hiring frenzy to bulk up long-understaffed review divisions. As we reported in an earlier blog post, the Center for Drugs Evaluation & Research will hire 663 employees—helped in large part by new money into FDA, as well as CDER director Janet Woodcock’s successful efforts to gain direct-hiring procedures from HHS.

Now, according to new information released by FDA to The RPM Report, CDER is nearly halfway through that hiring goal, having brought on 309 new employees so far this fiscal year (ending September 30). That's not an insignificant number for CDER to swallow: the center for drugs employed 2,252 individuals as of May 13.

But there’s good news for drug sponsors: at 108 employees, new hires into the Office of New Drugs have far outstripped any other CDER office. (That's to be expected, given that OND is the largest office in CDER, but it is still worth mentioning.) Plus, most of the hiring is within the divisions themselves, with few, if any, additions at the immediate office level. That means more division-level medical reviewers, and more time spent on new drug applications.

Some review divisions are benefiting from the hiring frenzy more than others, depending on the previous level of understaffing. Divisions with the most new hires are Gastroenterology Products, which has hired 16 employees so far this fiscal year, followed by Cardiovascular & Renal Products (9) and Neurology Products (8). All divisions, with the exception of Anti-Infective and Ophthalmology Products, has hired at least one new employee.

(For a handy chart with a division-by-division breakdown, click here. You can also access a summary breakdown of new hires across CDER by clicking here.)

While the hiring process itself is going quite well, CDER is also fighting attrition, as long-time FDA employees leave the agency, either for retirement or for more lucrative jobs in industry and academia. "We’re making progress, and we’re getting our head count up, but a miracle hasn’t occurred," Woodcock said in a recent interview with The RPM Report.

Indeed, several top-level FDA scientists have left for industry, including Robert Meyer, the former head of the Office of Drug Evaluation II, for Merck, and Mark Goldberger, the former director of the Office of Antimicrobial Products, for Abbott. Both departures came just weeks after the announcement that CDER director Steve Galson would be leaving to become surgeon general.

As USA Today reports in an article today, when companies siphon off FDA's most experienced scientists, they leave a leaner, less confident staff that is hesitant to approve new drugs. "What you have now is a big sucking sound of these staffers leaving FDA and going into the more lucrative side of the business or packing it in and retiring entirely," Steve Brozak, an analyst with WBB Securities, told USA Today. "This cannot have any positive effect whatsoever."

We have a slightly more optimistic outlook: In addition to the new hires, two other recent developments will help improve the regulatory environment for drug sponsors: 1) Woodcock's return to CDER; and 2) FDA's new REMS authorities. It won't happen overnight, but like Woodcock says, it's slow and steady progress.

Janet Woodcock’s To Do List For CDER

Given that Janet Woodcock has been back at the Center for Drug Evaluation & Research for six months now (with two months as permanent director), we figured it was high time to check in and see what she’s been up to.

The answer? Quite a bit.

As Woodcock told The RPM Report in an interview, she's the kind of person that likes to get things done. So upon returning to CDER last October, Woodcock settled on two immediate objectives:

(1) Gaining direct hire procedures from HHS’ Office of Personnel Management.

(2) Dedicating more attention on post-marketing safety.

Check and check.

As a result of Woodcock’s efforts, FDA just won direct-hiring procedures from HHS and has since embarked on a major hiring initiative to staff up its scientific ranks. CDER alone will hire 663 employees—444 new positions and 219 in backfill. The hiring frenzy will eventually help end the “lean years” at FDA, when the agency's regulatory mandate outstripped its available resources.

On post-marketing safety, Woodcock launched the “Safety First” initiative last October, putting post-marketing drug safety on par with new drug approvals. As part of that multidisciplinary, team-based approach, the Office of Surveillance & Epidemiology is now an “equal partner” with the Office of New Drugs. Remember those public fights over Avandia and Ketek? Woodcock hopes that "Safety First" will put those to rest.

Of course, there are still challenges ahead. CDER needs to train all those new hires, and the Center is still feeling its way on the “Safety First” initiative and implementation of the FDA Amendments Act in general.

And then there’s the issue of those new risk evaluation and mitigation strategies, or REMS, which have Woodcock weighing in on new drug applications more than usual. For more on that, as well as the status of drug approvals under her stewardship, click here. If you're not already a subscriber to The RPM Report, you can sign up for a free trial to view the article.

The Heat is On...The Hill

It may be springtime in Washington, but things just keep heating up for FDA and the pharmaceutical industry on Capitol Hill.

Heparin safety, the overseas inspections process, DTC advertising, FDA's budget and the integrity of the agency's scientific mission have all been the subject of one or more hearings so far this year.

Indeed, one influential member of Congress alone—Energy & Commerce Oversight & Investigations subcommittee chairman Bart Stupak—has already held four hearings related to pharmaceutical regulation. That doesn’t count his hearing today on DTC advertising and a crowded schedule in 2007, which included a two-part series on drug safety and a four-part series on food safety.

Center for New Drug Evaluation & Research director Janet Woodcock has shouldered more than her fair share of that hearing burden, testifying several times already this year, most recently on the heparin crisis and drug safety in general. She acknowledges the stress of the schedule she’s been keeping on Capitol Hill, but hopes that her testimony has helped put some issues to rest.

“We’ve had a good show for ourselves, at least at CDER,” she says. “We can get criticized, but I think we have answered the criticism, and that’s what we need to keep pressing on.”

One positive outcome may be more money for FDA: Sen. Ted Kennedy (D-Mass.) supports increasing FDA's fiscal 2009 appropriations by $375 million over FY 2008, with larger increases for the next five years. Commissioner Andrew von Eschenbach may have dampened enthusiasm for that big of an increase, however, by telling the Senate Appropriations Committee April 15 that FDA could absorb an additional $100 million in funding in FY 2009.

But the attention isn't all upside: We’ve said it before, but when FDA officials are hauled up to Capitol Hill and bashed over the head for doing a poor job, that doesn’t reflect too kindly on the industries it regulates. Woodcock expressed hope that the attention will start to shift to other issues. “They will continue to have oversight hearings,” she said, but “Congress will become more interested in the electoral process very soon.”

Well, not quite yet. FDA isn’t appearing at Rep. Stupak’s hearing on DTC advertising—executives from Pfizer, Merck/Schering Plough and Ortho Biotech are testifying today. But that doesn't mean they won't be next. We hate to say it, but this is exactly the kind of attention that we (ahem) predicted would happen following the Vytorin/Zetia kerfluffle. Given Rep. Stupak’s preference to hold multiple hearings on a single topic, you can bet it won’t be the last word.

The Other FDA Drug Chief

The drug industry is breathing a sigh of relief now that Janet Woodcock has permanently assumed the role as head of FDA's drug center.

But let's say Woodcock had turned down returning to oversee the Center for Drug Evaluation and Research, who would have been Commissioner Andrew von Eschenbach's next choice? Well, you can take a look at my incredibly accurate odds-making piece I wrote a few months ago. There were a number of internal candidates who may have been the choice. To read it, click here.

However, if von Eschenbach had decided to look outside, there were a number of names being thrown around as candidates. Two that I've mentioned before are Cornell pharmacologist Marcus Reidenberg and former University of Utah cardiologist Jeffrey Anderson. You can read a little more about them in The RPM Report by clicking here (registration required for non-subscribers).

Recently, I learned that another outside candidate was being pushed heavily by former FDA officials: Indiana University pharmacologist David Flockhart.

Flockhart appears to be exactly the type of candidate the agency would have been looking for in an external contender. Flockhart, chief of the division of clinical pharmacology at Indiana, is a believer in the personalized medicine revolution and the basic tenets behind FDA's Critical Path Initiative. To read more about his points of view on medicine, science, genetic testing and drug safety, click here.

A former Georgetown University researcher, Flockhart is credited with establishing Indiana as a site for NIH/National Institute of General Medical Sciences’ Pharmacogenetics Research Network. He received his MD from the University of Miami School of Medicine and PhD from the Welsh National School of Medicine in Cardiff.

So why does this matter? Well, it's interesting, isn't it? But more importantly, these are the types of thought leaders to keep on your radar for later down the road in different administrations or as possible liaisons between FDA and the academic world for key FDA/NIH/CMS initiatives. That's why they matter.

I'll keep my ear to the ground for other candidates that were interviewed or championed for the CDER director position so we can start a whole web series on "People Who Weren't Named CDER Director."

Finally, tune in next week for my Personalized Medicine Mailbag blog post. I wanted to thank everyone for the overwhelming response to my personalized medicine post. Apparently, people care about this issue. It's not too late to email me with your take on the personalized medicine vs. cost effectiveness debate.

Tort(i) Law: A Safe Pick for FDA

Perhaps the most significant thing to say about FDA’s new chief scientist is that there isn’t much significant to say about him.

In Frank M. Torti, a cancer researcher and professor at Wake Forest University School of Medicine, Andrew von Eschenbach appears to have selected a safe second-in-command during what has been a tumultuous time for the agency—an academic who is well-respected in his field and without apparent ties to industry.

As we pointed out previously, by choosing a non-confrontational academic to fill the vacant deputy commissioner post, von Eschenbach leaves open the possibility that the official might stay on at FDA under a new Administration, thereby extending the commissioner’s legacy after he leaves the agency.

But is Torti long for the job? According to his Wake Forest colleagues, the FDA appointment is more of a sabbatical than a permanent gig. Jerry Garvin, MD, who was named interim director of the cancer center in Torti’s absence, told the Winston-Salem Journal that he expects him to return to Wake Forest within nine months to a year. “He’s coming back,” Garvin told the paper. “Thank goodness.”

Of course, von Eschenbach originally joined FDA on what was assumed to be a temporary basis back in 2005, so maybe Torti will learn to love the position.

A initial focus of Torti’s role will be overseeing an important and relatively uncontroversial human resources initiative: FDA’s two-year fellowship program designed to attract and retain quality regulatory and scientific professionals.

The FDA Fellowship Program is a priority for von Eschenbach before he leaves the agency; the commissioner has been talking it up in recent appearances in Washington. The program will help FDA hire the 700 new people needed to fully staff the agency while at the same time helping to create a constituency empathetic to FDA’s challenges.

Torti’s office will also “work to ensure the quality and regulatory focus of the intramural research programs of the agency, and place special emphasis on the importance of clinical research trials that are a part of the foundation of the FDA’s regulatory structure,” the agency said.

It’s a vastly different set of responsibilities than those of Torti’s predecessor as deputy commissioner, Janet Woodcock. Before Woodcock became director of the Center for Drugs Evaluation & Research in March, the career official was all things to FDA: advocate for personalized medicine, champion of the Critical Path Initiative and chief implementer of the FDA Amendments Act.

In Torti, von Eschenbach has chosen a deputy commissioner with a background similar to his own. As the director of the Comprehensive Cancer Center at Wake Forest Medical Center, Torti specializes in genitourinary cancers. Von Eschenbach is himself oncologist and urologist, and is the former head of the University of Texas M.D. Anderson Cancer Center.

They also both have some experience in government service at the National Institutes of Health. Von Eschenbach served as head of the National Cancer Institute before joining FDA, while Torti is a member of NIH’s National Advisory Council for Complementary and Alternative Medicine.

So, OK. Maybe there are some things of significance to say about von Eschenbach’s newest hire. But unless we’re way off base here, it’s doubtful that the Torti Tenure will be too exciting for FDA—which is probably just what the doctor ordered.

FDA's Janet Woodcock: "Change Agent"

FDA Commissioner Andrew von Eschenbach expressed rare public irritability last week at the American Enterprise Institute.

What brought an edge to the voice of the usually unflappable, on-message commissioner? He bristled at the suggestion that the re-appointment of Janet Woodcock to head of the Center for Drug Evaluation & Research represents an attempt to rebuild the old ways of running the agency’s drug regulatory operations.

“I do not see her going back to CDER as business as usual,” von Eschenbach shot back in response to a question from a reporter during a Q&A session. She “is going back as a very, very strong change agent, and we have mapped and discussed many of those changes that she is embarking upon.”

Just because she has a long tenure in FDA management and is can be termed an “insider”, the commissioner said, “does not in any way, shape or form mean that she is not a change agent.”

For those that know the commissioner well, von Eschenbach’s sharp response came as a bit of a surprise. He generally maintains an unflappable demeanor and absorbs immense criticism for the agency and his management team without flinching. His restraint, in fact, is probably one of the factors in the constant beating on the agency in the media and on Capitol Hill.

So why get so irked about questions about the Woodcock appointment?

One answer is that von Eschenbach is worried that the staff within FDA is misinterpreting the appointment.

He says, in fact, that he has been “emphatic” within FDA in explaining his view of an active role for Woodcock at CDER. “The CDER that Dr. Woodcock will create for tomorrow is nothing like the CDER that she left,” he told the AEI forum.

Woodcock offers “understanding of the historical perspective as well as the external realities that are now impacting upon the agency,” the commissioner says (see here). She is “absolutely, the most extraordinarily gifted and talented person to lead” change at CDER, the commissioner told AEI.

Another reason for von Eschenbach’s pique is the lack of understanding from the outside world to the importance that he is putting on his end-of-term appointments at the agency. At this point on the down slope of his tenure at FDA, von Eschenbach appears to be viewing his recruitments and appointments to on-going agency management as one of his key lasting legacies for the agency.

The Woodcock appointment is “not the only appointment that has occurred and will occur at FDA; there will be others,” he declared. We have pointed out elsewhere the signs of stress and management holes within CDER (see here). FDA has a lot of mid-level and senior management positions to fill that will determine the character and focus of the agency through the next topside transition in early 2009.

Von Eschenbach stressed the need to “look at it in the totality of the kind of changes that are occurring both in staffing and in organizational structure and in the programs that we are implementing. In the totality of that, you will see the transformation that we are attempting to achieve.”

From the view of a lasting transformation, the Woodcock appointment is very savvy. She has identified herself in a court deposition as being a Democrat by political affiliation, but has clearly bought into one of the goals of the Bush Administration for FDA: to make the agency aware of changes that it can make to improve the drug development process–lumped for short-hand purposes under the sobriquet of the “Critical Path Initiative.”

By moving Woodcock off the commissioner’s staff to a line management position, von Eschenbach also opens up the possibility of recruiting someone for that deputy commissioner, chief medical officer position. If he can find someone to accept that position who has the credentials and political neutrality to survive a changeover of administrations, von Eschenbach may have a bigger role in shaping the post-election FDA.

Ex-FDA Commissioner Mark McClellan pointed out the key role for the chief medical office in a separate presentation at the AEI meeting. This is the job that was highlighted by the Institute of Medicine drug safety committee that reviewed and suggested structural changes needed at FDA in 2006. The position appeared to be designed for Woodcock, but now offers von Eschenbach a chance to find someone (probably from academia) who can try to survive the post-election changes.

McClellan told AEI that the deputy commissioner position could be a key slot for determining policy in the future. “The way you get the most done in the agency is to create a framework that enables people to get together and understand the weight of the scientific issues and get some scientific momentum behind the concepts and directions in which you want to take the agency,” McClellan said.

“Maybe the deputy commissioner for science at the agency…could bring together center directors and make sure that this gets built in consistently to what is going on in the agency.” McClellan said that driving policy at FDA takes a very hands-on consensus-building approach. It is like being a university president, he said. It cannot be achieved by “top-down directives.”

Instead, the management requires convincing “many people that are knowledgeable and pride themselves on being up-to-date on at least their particular area of expertise.” The commissioner cannot be expected to manage that process personally, McClellan suggested. The commissioner will have to rely on the next tier appointments–positions that von Eschenbach now has a chance to fill.

There is at least one other possibility why the commissioner reacted strongly at the AEI meeting: the question hit an exposed nerve. He senses that Woodcock will be challenged by FDA’s critics as a lame-duck appointment who will not have a significant impact.

And that view of FDA exists among knowledgeable people watching the agency. Former FDA Commissioner David Kessler was also at the AEI meeting. He sat silently, and unacknowledged, at the back of the room during the first day when von Eschenbach spoke. But on the second day, he quite pointedly spoke out from the dais about the state of leadership at the agency.

“I am interested in who is responsible for the leadership” on policy issues at FDA, Kessler declared. From practical experience, he suggested that the line operating heads at the agency cannot take time to deal with overall policy. “The center divisions have a lot on their plates,” he noted.

That leaves the challenge for guiding policy directly on the shoulders of the commissioner and his top staff. When does the commissioner's office get involved, Kessler asked. “Who is in charge on these broader policy questions? They are complex, they need to be driven. It is not just the day-to-day that you are dealing with.”

Maybe that is why von Eschenbach dropped his calm exterior for a moment. He knows that he is viewed as letting the agency float through a critical period. He is trying to assemble the right team for another FDA commissioner in the future, to try to influence a period even less under his control. That is a tricky and thankless task–one where a little anger is understandable.

If You Want a Job Done Right....

Well, this is a bit of a surprise.

After a lengthy search for a permanent head of FDA’s Center for Drugs Evaluation & Research, the agency is turning the reins over to an old hand—Janet Woodcock.

We admit it: like most of Washington, we didn’t see this one coming. While we wrote about the probability of a candidate emerging from inside FDA in last month’s issue of The RPM Report, we didn’t predict that Woodcock would be the final choice to head CDER.

But we take some comfort in the fact that no one else did either. For most folks in the policy world—including those on Capitol Hill—Woodcock’s return to CDER (she was director from 1994 to 2005) was a big surprise, and frankly, a bit of a head-scratcher.

After all, moving from the number-two spot at FDA to head the center for drugs could be seen as a demotion of sorts—especially since Woodcock was given a position in the commissioner’s office at a time when it was perceived that she might leave the agency altogether.

Rather than risk her leaving FDA altogether, Crawford gave Woodcock the title of deputy commissioner for operations and chief operating officer, and named Steven Galson to succeed her as CDER director. Under Andrew von Eschenbach, Woodcock became FDA's chief medical officer. But when Galson was tapped to be the acting Surgeon General, she stepped back in as acting head of CDER.

So if nothing else, relinquishing her commissioner office-level roles to become the permanent head of CDER frees up Woodcock's schedule a bit. According to FDA, the agency will be looking for someone to succeed her as deputy commissioner and chief medical officer. That may not be an easy task, given that the position of CMO was created precisely with her in mind after it was recommended by the Institute of Medicine in a review of the agency's drug safety programs.

So it comes as a bit of a shock that Woodcock is back in the director’s chair. But given that she was leading the CDER director search committee—and therefore ultimately picked herself as Galson’s successor—we assume she found enough good reasons to return.

Many point to a potential political advantage: as director of CDER, Woodcock will be well-positioned with the incoming Administration. Being outside the Office of the Commissioner will allow Woodcock to be viewed more as the career FDA official she is, rather than a political functionary of the outgoing Bush Administration.

But someone like Janet Woodcock doesn’t need to worry about playing politics to stay employable: there are plenty in industry and elsewhere who would welcome her with open arms—and a hefty pay raise. And people that know her well argue that she’s not the kind of person that would try to preserve her job at all costs.

Perhaps what Woodcock’s appointment really reflects is a commitment on her part to steer CDER through this time of transition. After all, there will be plenty of action in the drug center around the implementation of the FDA Amendments Act, a task Woodcock herself has acknowledged will be a unique and historical challenge.

Plus, she’ll be returning to CDER at a time when the future of the prescription drug user fee program is in question, so she’ll have an opportunity to fix the program that she first helped implement back in 1992. Indeed, the news that Office of New Drugs Director John Jenkins had given his medical reviewers the green light to slip a little on user fee deadlines may have helped push the CDER announcement along.

Plus—and let’s be frank here—given the resource and morale issues at CDER right now, who else would want that job? As one policy person we spoke to pointed out, there are only so many “buckets” of people that would even qualify.

FDA can’t bring in anyone that might appear to be conflicted, or risk the ire of Capitol Hill, so candidates with industry ties are out. That leaves either:

(1) academia. With CDER in such disarray, there are few academics with the management skills to steer the center through choppy waters; or

(2) current FDA officials. While CBER chief Jesse Goodman looked to be a solid pick to head the drugs center, Woodcock’s experience—and a thick skin that was on display at Rep. Rosa DeLauro’s appropriations hearing last month—ultimately helped make her the only viable choice.

For industry, this couldn’t be better news. Woodcock is well known by pharmaceutical and biotech manufacturers, and is certainly a familiar face to head CDER. While some critics question whether she is too cozy with industry, on the whole, she is seen outside the agency as a smart, honest and pragmatic leader.

The Pharmaceutical Research & Manufacturers of America issued a statement of strong support, noting her “willingness to work with diverse partners.” And one VP of global regulatory affairs, Amgen’s Paul Eisenberg, gave her a thumbs-up. When we asked him what type of person Woodcock should pick for CDER, he suggested that she should pick someone like herself. “She is really a leading driver for improvement of how FDA focuses on science and approvals," Eisenberg said.

Well, if the right prescription for FDA was to find someone just like Janet Woodcock to run CDER, then she certainly made the right choice.