Comments for FDA Matters http://www.fdamatters.com The Grossman FDA Report Mon, 06 Sep 2010 09:30:20 +0000 http://wordpress.org/?v=2.7.1 hourly 1 Comment on FDA to Industry: Contractors R U by FDA’s “Summer of Safety Concerns” « FDA Matters http://www.fdamatters.com/?p=989&cpage=1#comment-781 FDA’s “Summer of Safety Concerns” « FDA Matters Mon, 06 Sep 2010 03:40:45 +0000 http://www.fdamatters.com/?p=989#comment-781 [...] FDA to Industry: Contractors R U June 17th, 2010 [...] [...] FDA to Industry: Contractors R U June 17th, 2010 [...]

]]> Comment on “Safe”: Many Meanings Complicate FDA Policymaking by FDA’s “Summer of Safety Concerns” « FDA Matters http://www.fdamatters.com/?p=942&cpage=1#comment-780 FDA’s “Summer of Safety Concerns” « FDA Matters Mon, 06 Sep 2010 03:40:30 +0000 http://www.fdamatters.com/?p=942#comment-780 [...] laid out in more detail in “Safe”: Many Meanings Complicate FDA Policymaking, there is a strong tendency to think of FDA’s safety mission as if it were one type of [...] [...] laid out in more detail in “Safe”: Many Meanings Complicate FDA Policymaking, there is a strong tendency to think of FDA’s safety mission as if it were one type of [...]

]]> Comment on Late Friday Afternoon: FDA, Politics, and Scientific Integrity by Steven Grossman http://www.fdamatters.com/?p=1059&cpage=1#comment-750 Steven Grossman Mon, 16 Aug 2010 14:00:54 +0000 http://www.fdamatters.com/?p=1059#comment-750 A reader from outside FDA but knowledgeable about Ella has written to say: "You made the assumption that FDA held off on the press release until late Friday afternoon to avoid attention. That is incorrect. Friday was the PDUFA date for the product and there was a lot of activity going on up until the moment the action letter was sent to the sponsor." I do not have specific knowledge of FDA's situation late last week. The column is built on my reaction to the timing of the release and may have inaccurately ascribed motives to FDA that they didn't have. Since FDA releases have to be written and cleared in advance, it is certainly possible that, as my reader suggests, the timing last week was driven by when the review division finished their work and issued the approval letter. The division could also have been conscious of the value of finalizing the approval on Friday, but since it was the PDUFA deadline there is no basis to draw that conclusion. Ultimately, the article is about politics and science. My point is that there are instances when science is not sufficient to decide questions. FDA is not immune to this tenstion. Plan B approval for Rx is largely a scientific issue, while over-the-counter availability is not. Ultimately, OTC availability of Plan B was decided by a court and Obama Administration officials chose not to appeal the decision. Did the Bush Administration's handling of the OTC application compromise the agency? I would agree it did. But beyond this egregious example, FDA is still an agency that did and still does the best job it can, recognizing that many decisions will be controversial and some will turn out badly. I am very impressed by Dr. Hamburg during her first 15 months.. Her commitment to "science-based decisionmaking" is laudable and welcome. Yet, it will not keep her out of controversy in which the agency's use and interpretation of science is called into question. I can't say for sure what that issue will be, but the possibilities include Avandia, the alleged food-surface contaminent BPA, and the revsion of medical device approval standards. A reader from outside FDA but knowledgeable about Ella has written to say: “You made the assumption that FDA held off on the press release until late Friday afternoon to avoid attention. That is incorrect. Friday was the PDUFA date for the product and there was a lot of activity going on up until the moment the action letter was sent to the sponsor.”

I do not have specific knowledge of FDA’s situation late last week. The column is built on my reaction to the timing of the release and may have inaccurately ascribed motives to FDA that they didn’t have. Since FDA releases have to be written and cleared in advance, it is certainly possible that, as my reader suggests, the timing last week was driven by when the review division finished their work and issued the approval letter. The division could also have been conscious of the value of finalizing the approval on Friday, but since it was the PDUFA deadline there is no basis to draw that conclusion.

Ultimately, the article is about politics and science. My point is that there are instances when science is not sufficient to decide questions. FDA is not immune to this tenstion. Plan B approval for Rx is largely a scientific issue, while over-the-counter availability is not. Ultimately, OTC availability of Plan B was decided by a court and Obama Administration officials chose not to appeal the decision.

Did the Bush Administration’s handling of the OTC application compromise the agency? I would agree it did. But beyond this egregious example, FDA is still an agency that did and still does the best job it can, recognizing that many decisions will be controversial and some will turn out badly. I am very impressed by Dr. Hamburg during her first 15 months.. Her commitment to “science-based decisionmaking” is laudable and welcome. Yet, it will not keep her out of controversy in which the agency’s use and interpretation of science is called into question. I can’t say for sure what that issue will be, but the possibilities include Avandia, the alleged food-surface contaminent BPA, and the revsion of medical device approval standards.

]]> Comment on When Abbreviated May Not Mean Faster or Easier by Steven Grossman http://www.fdamatters.com/?p=1042&cpage=1#comment-714 Steven Grossman Mon, 26 Jul 2010 13:59:28 +0000 http://www.fdamatters.com/?p=1042#comment-714 Based on e-mails this morning, there is a lot of interest in accelerated approvals. One reader pointed out that the FDA has faced failed results twice in a short period of time. The first drug was withdrawn by Pfizer. The second (the one I was referencing) faced an advisory committee last week and the panel recommended that FDA withdraw approval for a specific indication of the drug. The Roche drug, Avastin, is already marketed for indications that were approved through regular, not abbreviated, process. At stake is this additional indication that was approved via the accelerated approval process. To my knowledge, FDA has not announced any review of the policies and processes associated with accelerated approval, but I stand by my prediction that this will happen soon. For a good background, I recommend this article from PharmaLot, which provides excellent daily coverage of FDA and industry activities: http://www.pharmalot.com/2010/07/fda-panel-votes-down-avastin-for-breast-cancer/ For a glimpse of some of the heat being generated by this issue, I suggest this editorial from today's NY Times: http://www.nytimes.com/2010/07/26/opinion/26mon1.html?_r=1&emc=tnt&tntemail1=y Based on e-mails this morning, there is a lot of interest in accelerated approvals. One reader pointed out that the FDA has faced failed results twice in a short period of time. The first drug was withdrawn by Pfizer. The second (the one I was referencing) faced an advisory committee last week and the panel recommended that FDA withdraw approval for a specific indication of the drug. The Roche drug, Avastin, is already marketed for indications that were approved through regular, not abbreviated, process. At stake is this additional indication that was approved via the accelerated approval process. To my knowledge, FDA has not announced any review of the policies and processes associated with accelerated approval, but I stand by my prediction that this will happen soon.

For a good background, I recommend this article from PharmaLot, which provides excellent daily coverage of FDA and industry activities: http://www.pharmalot.com/2010/07/fda-panel-votes-down-avastin-for-breast-cancer/

For a glimpse of some of the heat being generated by this issue, I suggest this editorial from today’s NY Times: http://www.nytimes.com/2010/07/26/opinion/26mon1.html?_r=1&emc=tnt&tntemail1=y

]]> Comment on FDA, Female Sexual Desire and the Media by Steven Grossman http://www.fdamatters.com/?p=1018&cpage=1#comment-666 Steven Grossman Mon, 28 Jun 2010 14:55:49 +0000 http://www.fdamatters.com/?p=1018#comment-666 Not to pick on just the NY Times....the LA Times story has similar failings: http://www.latimes.com/news/health/la-he-female-viagra-20100628,0,2320200.story?track=rss&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+latimes%2Ffeatures%2Fhealth+%28L.A.+Times+-+Health%29. Not to pick on just the NY Times….the LA Times story has similar failings:
http://www.latimes.com/news/health/la-he-female-viagra-20100628,0,2320200.story?track=rss&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+latimes%2Ffeatures%2Fhealth+%28L.A.+Times+-+Health%29.

]]> Comment on FDA to Industry: Contractors R U by Steven Grossman http://www.fdamatters.com/?p=989&cpage=1#comment-658 Steven Grossman Tue, 22 Jun 2010 13:49:59 +0000 http://www.fdamatters.com/?p=989#comment-658 The New York Times has a news story about oversight of foreign clinical trials. Again, it is evidence that the DHHS IG (with FDA agreeing) believes that drug companies are not overseeing their vendors (the overseas clinical trial sites). Running clinical trial sites (US and ex-US) is a business and company to trial site is a business relationship. HHS Report Incites Concern Over Foreign Drug Trials. The New York Times (6/22, A14, Harris) reports that "Daniel R. Levinson, the inspector general of the Department of Health and Human Services," will release a report on Tuesday that found "80 percent of the drugs approved for sale in 2008 had trials in foreign countries, and 78 percent of all subjects who participated in clinical trials were enrolled at foreign sites." But Levinson "pointed out that the [FDA] was often unaware of foreign clinical trials as they were being conducted. As a result, federal regulators have no ability to ensure that patients in these trials are being protected while the research is continuing." Rep. Rosa DeLauro (D-CT) said, "By pursuing clinical trials in foreign countries with lower standards and where F.D.A. lacks oversight, the industry is seeking the path of least resistance toward lower costs and higher profits to the detriment of public health." The Times also notes that "the F.D.A. was unable to provide Mr. Levinson's investigators with detailed clinical trial data for 29 of the 129 of the approved applications in 2008." The New York Times has a news story about oversight of foreign clinical trials. Again, it is evidence that the DHHS IG (with FDA agreeing) believes that drug companies are not overseeing their vendors (the overseas clinical trial sites). Running clinical trial sites (US and ex-US) is a business and company to trial site is a business relationship.

HHS Report Incites Concern Over Foreign Drug Trials.
The New York Times (6/22, A14, Harris) reports that “Daniel R. Levinson, the inspector general of the Department of Health and Human Services,” will release a report on Tuesday that found “80 percent of the drugs approved for sale in 2008 had trials in foreign countries, and 78 percent of all subjects who participated in clinical trials were enrolled at foreign sites.” But Levinson “pointed out that the [FDA] was often unaware of foreign clinical trials as they were being conducted. As a result, federal regulators have no ability to ensure that patients in these trials are being protected while the research is continuing.” Rep. Rosa DeLauro (D-CT) said, “By pursuing clinical trials in foreign countries with lower standards and where F.D.A. lacks oversight, the industry is seeking the path of least resistance toward lower costs and higher profits to the detriment of public health.” The Times also notes that “the F.D.A. was unable to provide Mr. Levinson’s investigators with detailed clinical trial data for 29 of the 129 of the approved applications in 2008.”

]]> Comment on “Safe”: Many Meanings Complicate FDA Policymaking by Steven Grossman http://www.fdamatters.com/?p=942&cpage=1#comment-615 Steven Grossman Tue, 25 May 2010 17:31:32 +0000 http://www.fdamatters.com/?p=942#comment-615 Eric---Thank you. I did write this more from the perspective of the FDA-Congress-media dialog where imprecision about safety has policy consequences. I think the Commissioner and the resource-deficient agency would do better if they articulated how the mandate for safe food and medical products has many parts that must be serviced separately. I would hope that my column would put to rest any notions that the agency would be more effective if it had a safety czar or a safety center or any kind of uber- centralization of safety functions. Some consolidation might be good, but there are far too many parts for which this is not a good idea.. The manufacturer's perspective is a useful one. I have written previously "in praise of predictability." http://www.fdamatters.com/?p=467. For a lot of companies that doesn't seem to be enough. A significant amount of safety problems seem to be in cases where the company knew or should have known better. This makes me wonder whether there is a degree of operational imprecision internal to companies. When the CEO asks: are our products safe?....he might get a more nuanced answer and better responsiveness if it were three or four questions that focused on different aspects of what makes a product safe. Steven Eric—Thank you. I did write this more from the perspective of the FDA-Congress-media dialog where imprecision about safety has policy consequences. I think the Commissioner and the resource-deficient agency would do better if they articulated how the mandate for safe food and medical products has many parts that must be serviced separately. I would hope that my column would put to rest any notions that the agency would be more effective if it had a safety czar or a safety center or any kind of uber- centralization of safety functions. Some consolidation might be good, but there are far too many parts for which this is not a good idea..

The manufacturer’s perspective is a useful one. I have written previously “in praise of predictability.” http://www.fdamatters.com/?p=467. For a lot of companies that doesn’t seem to be enough. A significant amount of safety problems seem to be in cases where the company knew or should have known better. This makes me wonder whether there is a degree of operational imprecision internal to companies. When the CEO asks: are our products safe?….he might get a more nuanced answer and better responsiveness if it were three or four questions that focused on different aspects of what makes a product safe. Steven

]]> Comment on “Safe”: Many Meanings Complicate FDA Policymaking by briut http://www.fdamatters.com/?p=942&cpage=1#comment-607 briut Mon, 24 May 2010 15:54:17 +0000 http://www.fdamatters.com/?p=942#comment-607 Steven, Insightful post. You're always a pleasure to read. For me, the question of definition is really just an OPERATIONAL one. A "safe" and effective drug (generally) means two well-controlled studies. For generally recognized as "safe" foods, the standard is basically just showing a good track record. Other unique definitions for "safe" devices (remember breast implants?), "safe" fast-tracking for cancer/AIDS drugs, and so on. Frankly, I don't mind so much that one word means so many things (or, as in Alice in Wonderland, whatever I want it to mean). I just want to know what the standard is so I can show my clients the height of the hurdle. "Tell me the rule, (tell me it's being applied fairly to my competitors, as well,) and I'll do it." Unless, of course, you'd like to write FDA a new lexicon, which wouldn't be such a bad idea as you seem to suggest.... - Eric Katz Steven,
Insightful post. You’re always a pleasure to read. For me, the question of definition is really just an OPERATIONAL one. A “safe” and effective drug (generally) means two well-controlled studies. For generally recognized as “safe” foods, the standard is basically just showing a good track record. Other unique definitions for “safe” devices (remember breast implants?), “safe” fast-tracking for cancer/AIDS drugs, and so on.

Frankly, I don’t mind so much that one word means so many things (or, as in Alice in Wonderland, whatever I want it to mean). I just want to know what the standard is so I can show my clients the height of the hurdle. “Tell me the rule, (tell me it’s being applied fairly to my competitors, as well,) and I’ll do it.” Unless, of course, you’d like to write FDA a new lexicon, which wouldn’t be such a bad idea as you seem to suggest…. - Eric Katz

]]> Comment on Orphan Drugs and Bio-Similars: Is 12 Better than 7? by Steven Grossman http://www.fdamatters.com/?p=937&cpage=1#comment-599 Steven Grossman Mon, 24 May 2010 03:38:40 +0000 http://www.fdamatters.com/?p=937#comment-599 Mary---For most rare diseases, you are correct. It's hard enought to get one company interested, impossible to imagine competition. But for a small but growing number of rare diseases, there is one very expensive orphan drug and one or more companies interested in competing with them. For a rare disease without any good treatments, it can be a cruel twist to see that the orphan drugs in their future are going to be expensive. If given a choice, I think most individuals with rare diseases would prefer the treatment be developed, anyway. It is a positive sign for patients that others might want to compete with a bio-similar product, which should drive prices down by 15% to 30%. Your other points about clinical trials and approval standards for orphan drugs are appropriate. This is a topic I will explore in a future column. Steven Mary—For most rare diseases, you are correct. It’s hard enought to get one company interested, impossible to imagine competition. But for a small but growing number of rare diseases, there is one very expensive orphan drug and one or more companies interested in competing with them. For a rare disease without any good treatments, it can be a cruel twist to see that the orphan drugs in their future are going to be expensive. If given a choice, I think most individuals with rare diseases would prefer the treatment be developed, anyway. It is a positive sign for patients that others might want to compete with a bio-similar product, which should drive prices down by 15% to 30%.

Your other points about clinical trials and approval standards for orphan drugs are appropriate. This is a topic I will explore in a future column. Steven

]]> Comment on Orphan Drugs and Bio-Similars: Is 12 Better than 7? by mgraper http://www.fdamatters.com/?p=937&cpage=1#comment-595 mgraper Sun, 23 May 2010 23:59:16 +0000 http://www.fdamatters.com/?p=937#comment-595 Does 12 vs 7 years really matter when we are talking about orphan drugs? We in the orphan disease business are fortunate that even one pharma has agreed to develop a drug to help these patients. I can't imagine any other pharma wanting to develop a bio-similar drug given the costs and years involved in doing so. There is just simply not that much market competition out there for "us". However, I do believe that the FDA should slack up a bit on what is required to bring an orphan drug to market. There are simply not enough patients around to satisfy the FDA's current requirements for all of the phases and cohorts of study patients that is required. There should certainly be stringent safety measures, yes. But, if "we" are to help those small groups of orphans to seek treatments and/or a cure, surely there must be a better way. Does 12 vs 7 years really matter when we are talking about orphan drugs? We in the orphan disease business are fortunate that even one pharma has agreed to develop a drug to help these patients. I can’t imagine any other pharma wanting to develop a bio-similar drug given the costs and years involved in doing so. There is just simply not that much market competition out there for “us”.
However, I do believe that the FDA should slack up a bit on what is required to bring an orphan drug to market. There are simply not enough patients around to satisfy the FDA’s current requirements for all of the phases and cohorts of study patients that is required. There should certainly be stringent safety measures, yes. But, if “we” are to help those small groups of orphans to seek treatments and/or a cure, surely there must be a better way.

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