FDA Warnings Double In Obama’s First Year
24 CommentsBy Ed Silverman // February 2nd, 2010 // 8:34 am
The number of FDA warnings issued for questionable promotions has nearly doubled since President Obama took office. The agency sent 41 enforcement letters in 2009, up from 21 in 2008, according to Tom Abrams, who heads the agency’s Division of Drug Marketing, Advertising and Communications. Meanwhile, nine letters were sent just last month (see here and here).
“We’re trying to get the point across to industry that we want them to comply with the law because it affects public health. If you don’t comply with the law, we are going to take action. We are not going to tolerate having consumers or healthcare professionals misled,” Abrams told Reuters, citing an edict from FDA commish Margaret Hamburg. “We are inspired by Dr. Hamburg’s enforcement initiative and have taken it to heart,” he said. “I personally am thrilled with it.”
Mark Senak
Hi. While true, the actual number did go up, 14 of those letters represent the anomaly of the 14 letters issued regarding paid search on April 2. If you take those out, it was not such a red letter year. See my posting on same - http://www.eyeonfda.com/eye_on_fda/2010/02/warning-letters-double-or-spin.html
Condor
Hello Mark –
With all due respect, I will politely disagree. The sea has changed — on warnings — at FDA.
I think 40 to 60 warning letters per year, is “the new normal.” [New, but entirely Public Domain graphics plainly included -- grab 'em while they're hot.]
Namaste — great stuff, Ed!
Doc
The FDA is so overworked, they unfortunately can only go after the most egregious cases, there are many off label cases that have done and continue to do real patient harm, but they are below the public’s radar.
Too bad.
Condor
Indeed, Doc. My experiences would dovetail with your own.
Namaste
Justice in MI
Just took a brief scan, but few of these warnings appear related to off-label but rather other promo violations.
DDMAC does appear revived, especially since the Bush era.
Question is: what difference does it make? On another recent thread, some suggested that getting such letters was almost a badge of doing your job. And by the time they appeared, there would be a new campaign going in any case…
Condor
JiM — While I agree that few in pharma seem as mortified about such letters as they were in say, the 1970s — I do think the letters tend to have a cumulative effect (even if it is just within the agency — FDA).
I certainly see evidence that companies with multiple unresolved warning letters are likely to experience far longer waiting-line-times, to FDA-new-drug-approvals — if the approval comes at all.
That alone (often reflecting figures in the hundreds of million range — of dollars of lost, or delayed) should garner the CEO’s rapt attention (or perhaps, the CEO-In-Waiting’s attention — Ken Fraizer).
Namaste
ex-FDA
If DDMAC letters have any relationship at all to NDA approval times it’s only because it signifies issues of quality across the board within a company. Within FDA the review divisions are unaware of letters from DDMAC to sponsors. Even in the rare instances we are aware of them due the press they do not effect the review decisions of NDAs. The review times and review decisions of reviewers are independent of anything that occur with DDMAC. The only time I ever saw other issues holding up an approval is when it’s for a supplemental approval and there are other issues with the same drug such that the sNDA could be used to open requests to address these other issues, e.g. a drug interaction, safety, or labeling issue that had previously been overlooked.
Condor
Fair enough Ex-FDA –
I think my experience would suggest that companies with multiple unresoved 482’s and warning letters are companies with compliance problems generally.
Thus those companies’ NDAs face longer timelines to approval — due to the companies’ own shortcomings.
Namaste
harpy
I would think that companies with lots of warning letters should be looking out for DoJ, not FDA. They don’t look too good for establishing a “culture of compliance” in this climate.
patrons99
I agree, Harpy. FDA is generally “toothless”…all bark, no bite. Warnings won’t get it done. Large fines and civil “misdemeanors” won’t get it done. It will require political will from the top of DOJ to the bottom and criminal sanctions to ever stop the “crime spree”.
pharmavet
I provide as a public service:
http://www.forbes.com/2010/02/02/drug-advertising-lipitor-lifestyle-health-pharmaceuticals-safety_slide_2.html
BP Doc
Fantastic news! Please keep up the heat. Much more has to be done, but it’s a start. The BP companies have been getting away with murder for too long. Follow-through with trials and personal fines to the cheating execs will be needed in order to change their MO.
patrons99
Condor and ex-FDA:
You both seem be making diametrically opposite statements:
Evidentally, one of you (Condor) believes that NDAs and sNDAs may be stonewalled somewhat and the other (exFDAer) says that there is really no effect on the timelines to approval. Which is it?
I thought that timelines to approval are strictly defined under the serial reenactments of the PDUFA. So, ultimately, this would seem to me to indicate that “warning letters” from FDA will have no real effect on time to approval.
As we all know, time in the marketplace, is literally worth billions to pharma. Once the expedited approvals are gained under the PDUFA, the illegal off-label marketing begins very soon thereafter, if not immediately.
Condor
I am not so sure, patrons99. . .
All FDA need do is declare a given New Drug Application “incomplete” in any number of material respects, and all the clocks get reset. [And to be clear, my experience is that this happens more commonly to companies with lots of unresolved and pending 483's and warning letters. I think Ex-FDAer is right that it is more a funciton of poor compliance generally at such companies, than any form of an FDA would-be "vendetta" -- those are imaginary. Like unicorns.]
For example, FDA may take a preliminary look at an NDA packet, and simply say the submitted data-sets are inadequate to support the indication for which the NDA is submitted.
That is how this generally works, in my experience — once a company gets a reputation for low quality — it tends to persist.
Namaste
ScottRPh
So, the FDAs reaction to companies it does not like due to real or imagined quality issues, is to find a bureaucratic reason to delay new and useful medications to the American public. So much for keeping the patient’ health and safety front of mind at the FDA.
The other thing I don’t understand is why the FDA thinks that a cheerleader with a BA in communication with a couple months of training can totally confuse and misdirect a physician with 8-10 years of medical education, plus years of practice experience, about treating their patients efficiently and as safely as possible. Not to mention the ethical and legal ramifications for the individual physician. It would be like one of you guys going to a car dealership to by a Prius for commuting to work and the salesperson convinces you to buy a Ford 350 pick-up truck. Not very likely, is it. Maybe it was all those Pens and Pads with product names on them that sway them. I mean when you get a calendar from your local bank or real estate agent, don’t you immediately run out the door to get a lone and buy a new house?
patrons99
I liken FDA drug approvals to a race between a tortoise and a hare. It’s very much a rigged contest in which the hare (pharma’s NDAs) invariably make it to the finish line (market approval) before the tortoise (regulatory sanctions and/or formal legal proceedings for research fraud) ever makes it out of the starting blocks. Actually, under the PDUFA, the hare is virtually jet-propelled (on nitro) to market approvals. Amazing how that legislative enactment (the PDUFA) came to pass. All for the greater social good, of course. It’s really all about time in the marketplace. Drug safety and efficacy are superfluous.
Condor
ScottRPh — you write:
“. . . .So, the FDAs reaction to companies it does not like due to real or imagined quality issues, is to find a bureaucratic reason to delay new and useful medications to the American public. . . .”
No one (in this thread) wrote any of that. Do try to stay awake next time.
The rest of yours merits little response, inasmuchas you depart from a fundamentally-flawed premise.
Namaste, just the same.
ex-FDA
I don’t think that Condor and I are at odds at all. We are basicly saying the same thing. Companies that have lots of 483’s and warning letters have lots of problems in general and that parallels problems that that may delay FDA approvals. That does not mean that FDA says you have lots of warning letters and so you we will be tougher on you.
As for how things really work. What Condor is referring to that resets the clock is a refusal to file. A refusal to file only occurs when the application itself is so blatently deficient that the the company clearly did not include studies that everyone knows are absolutely required for review, i.e. if there is no data to review how can you even start the review.
For example 2 positive clinical studies are required for approval, however even if the company submits 1 positive and 1 negative study (and even admits at submission that 1 of the studies is negative) the application still needs to be reviewed and cannot be refused. A company may do this just to buoy the stock price or for other reasons (bonuses for submission by a certain date) and then blame the FDA when it’s turned down.
If an NDA is not filed it then has to be reviewed at the highest levels of the agency and I can tell you from personal experience that division directors are absolutely terrified of this and will do everything possible not to refuse a filing.
483s tend to be warning letters for manufacturing issues. Before an NDA is approved an inspection of the manufacturing plant has to take place. Since plants tend to manufacture many drugs, if a plant already has multiple problems and multiple 483’s (e.g. there’s dirty water dripping from the ceiling in the storage area onto open barrels of drugs waiting to be packaged) it’s unlikely to be able to pass the pre-approval inspection because those problems will likely also apply to the new drug and that will preclude approval of the manufacturing facility. So like I said there may be an association between ongoing problems and delays in approval, and in particular as related to field inspections, but at the division level with the reviewers who actually look at the submission data itself (i.e. clinical, pharmacology, chemistry, clinical pharmacology, statistics) there is no connection between warning letters and approval decisions.
Remember association does not mean cause and effect.
Also note that warning letters for manufacturing issues are in an entirely different category than warning letters for advertising.
Condor
Well put, Ex-FDA — thanks for straightening us out — and clarifying mine. Yours does a much better job, at that.
And, though not precisely the core topic of this particular thread, it is certainly true that unresolved 483’s often cause a “cascading effect” on various other aspects of regulatory compliance — not least of which is clearing any NDA for a drug proposed to be manuafactured in the same physical facility.
Namaste
Josh
As someone in the manufacturing side of the industry (compliance), I can attest that there is a huge difference between a DDMAC and a manufacturing warning letter. Manufacturing arms of companies fear WL’s and 483’s, I know we do. A repeat and/or unresolved 483 is a huge no-no for a manufacturer….warning letter material.
And as a FYI, not all NDA’s require a PAI.
I do know of a few companies that have had consent decrees and’or import blocks and still get approvals through….I can tell you that it does piss off the companies that are doing it right (we have had abbreviated GMP inspections because of our good regulatory inspection history).
pharmavet
Josh is right. Just ask Abbott Diagnostics or Genzyme more recently.
JaT
Sorry, but from the outside looking in, this convo is a little funny.
“Since pilot-scale manufacturing facilities are not available at the FDA, this collaboration provides the Agency with an opportunity to conduct on-line research related to the implementation and validation of PAT tools. It also provides access to Pfizer’s industry leading expertise in the area of on-line PAT and chemical imaging of pharmaceutical products.”
I wonder if that has been rectified. Evidently CRADA trumps the regular approval process- which I could show (again) if it would matter at all. So far it has not.
~shrug~
Hulk
Genzyme. Killed mommy. Make Hulk mad.
Hulk
Condor
Hello laura — I think “Hulk” is displaying an ironic sense of humor. I don’t share it, but I do think, in some fashion, Hulk means to refer to this:
. . .A series of stumbles, particularly manufacturing problems, has sent Genzyme’s stock to its lowest level in five years, angering investors and leaving patients without medicines they desperately need.
The pressure on Mr. Termeer intensified Monday with the news that Carl C. Icahn, the billionaire activist investor, is seeking a seat for himself and three associates on Genzyme’s nine-member board at the company’s annual meeting in May.
Mr. Icahn has not yet indicated what his ideas for the company are, nor which four of Genzyme’s current directors he would want his own candidates to replace, something he will have to specify eventually.
Mr. Icahn’s move could put pressure on the company to sell itself or divest itself of some of its varied businesses. And, in cases when Mr. Icahn does win seats on a board, the chief executive’s exit sometimes follows. . . .
So, (1) Henri A. Termeer, CEO of Genzyme, is under fire — and from none other than Carl Icahn — Icahn’s funds have taken a large stake in Genzyme and are lobbying for the ouster of CEO Termeer (i.e., “Killed Mommy“!?).
(2) Ichan is seeking seats on the board, and the board recently restructured governance roles, and voted NOT to pay Termeer a bonus for this past year (i.e., Icahn/Board = “Make HULK mad.”)
So, I think there is actually a little bit less here than appears. . . .
In any event, doubt we’ll see “Hulk” again, anytime soon.
Namaste