QDIS Blog

Wow, I must say I was very much surprised to learn this morning that the FDA has approved Sandoz’s generic version of the human growth hormone Omnitrope ® (somatropin). Here is a link to the page that contains the press release.

Sandoz gets precedent-setting US approval for Omnitrope®

Here is The Generic Pharmaceutical Association (GPhA) view of things from Yahoo finance.

GPhA Hails Omnitrope Approval

They claim that this proves there is indeed a “pathway to approval” for biogenerics.

I’ve written about generic biologics previously. I really think this may be a mistake. Approving a biogeneric without some kind of process in place is just asking for trouble in the future. While I realize that Sandoz has spent some time and effort in the development and has been waiting for quite some time, it still doesn’t make sense to approve a biogeneric without a process in place. My experience with most companies and projects that are new and don’t have at least a basic mutual understanding of what is required are usually either doomed to failure, or end up in a lawsuit. This one is already starting with a lawsuit since Sandoz had to sue the FDA to get them to act.

The FDA has posted a Q&A page on Omnitrope and here they lay out their rational behind the decision and classify it as a “follow-on protein product”. They specifically state that it is not a generic biologic. Here the pertinent part:

Is Omnitrope a generic biologic?

No. Omnitrope is not rated as therapeutically equivalent to (and therefore substitutable for) any of the other approved human growth hormone products. Omnitrope is more appropriately characterized as a “follow-on protein product.”

I’m not sure how this is going to shake out with other companies that are contemplating introducing biogenerics (or should I say “follow-on protein products”). I can only hope that the FDA will put together guidance documents out for those who are considering “follow-on protein products” (FOPP?). I still think biogenerics sounds better. FOPP just has sounds negative to me; too much like flop. And no one is going to spell out “follow-on protein product” every time.

Other sources for news on this:

• USATODAY.com - FDA approves growth hormone
• from the SF Chronicle: FDA Approves Growth Hormone
• Novartis wins landmark US biogeneric approval - Yahoo! News

Technorati Tags: biogenerics, FDA, somatropin

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Mark Senak over at Eye on FDA posted about the possibility of a recess appointment for current acting FDA commissioner Andrew C. von Eschenbach. He makes some very good points and I tend to agree with him concerning the possible damage to the FDA if Dr. von Eschenbach should be appointed during a congressional recess.

By opinion though is the current administration really doesn’t care about that. The same argument applies to John Bolton and his appointment to the UN. I think there is a real possibility this will indeed happen especially since, as Mark point out, Dr. von Eschenbach has already resigned from his post at the NIH. I’m sure the administration has given him some sort of “guarantee” before he resigned form the NIH. I also think that if a recess appointment does occur, Dr. von Eschenbach will almost certainly be another short-time leader of the FDA. I really think this is too bad but that’s how I read the tea leaves at the current time.

Technorati Tags: FDA

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Although this was published earlier this month, I just came across it. This article indicates that doctors are indeed concerned about new drugs and this is indicated by the drop in prescriptions for antidepressants and COX-2 inhibitors.

Survey Reveals Seven Out of 10 Doctors Concerned About Safety of Prescription Medicines

I know from personal experience, my family physician is very hesitant to prescribe any new drugs, especially those that have been on the market less than one year. He prefers to wait and see if there are any problems. Now this does suppose that any problems would be revealed in the first year and that may not be the case. As always, it’s a mater of balancing the risk vs reward.

Also generics are generally looked upon as safe since they have stood the test of time. The reasoning goes that having been around for some time, any problems would have been identified by now. I tend to agree with this but still think it needs to be said that no drug is without risks. Also, second and third generation drugs (i.e. newer ones) sometimes have less side effects. The best know case are the antihistamines. The first generation such as Benadryl (diphenhydramine) caused drowsiness. However, newer antihistamines such as Claritin (loratidine), Zyrtec (cetirizine), and Allegra (fexofenadine) did not show this tendency.

Another interesting fact was looking at various groups views towards new drugs; 33% of physicians thought new or recently approved drugs were less safe, 29% of consumers felt this way, and 26% of pharmacists feel that way.

Technorati Tags: drug safety

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Just wanted to let folks know that they no longer have to register before being able to add comments. Hopefully this change will make it easier for folks to post comments. Note that comments are moderated.

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Here’s an interesting item that somehow escaped me when it was announced and I just now heard about it. Seems Dishman Pharmaceuticals & Chemicals Ltd will purchase the pharmaceutical services division of Solutia (Carbogen and Amcis) for $74.5 million.

• The Hindu Business Line : Dishman to buy Swiss co Solutia’s unit

I had known that Solutia was looking to sell this unit a year or so ago but, Solutia then changed their mind and wasn’t going to sell the pharma unit. In the Sept 5, 2005 issue of Chemical and Engineering News under business concentrates, they announced the sale of the consulting arm to Paul Woitach (Pharmaceutical Advisors) but at the end of that short article it states that earlier this year (2005) Solutia decided to hold on to these businesses. Seems they didn’t stick to that decision for very long.

Since I have people I know who work at both Carbogen and Amcis and have done projects with them in the past I truly hope things work out for the best for them. I have always had a pleasant experience in my dealings with them and hope that doesn’t change.

Indian pharmaceutical companies seem to be buying up contract manufacturers of late. Recently, Shasun Chemicals & Drugs bought Rhodia.

• Shasun acquires Rhodia Pharma custom synthesis business

Avecia also sold their contract manufacturing to Nicholas Piramal India Ltd back in Oct of 2005.

• The Hindu Business Line : Nicholas Piramal buys Avecia

I think this shows how serious the pharma industry in India is in being seen by the world as a leading player in the pharma arena. With all the growth in outsourcing and India being one of those places these acquisitions make sense.

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Just wanted to see if anyone out there who reads this would have any interest in a podcast of pharmaceutical news? I am toying with the idea of starting a second podcast (I already do the Searching the Internet podcast about finding information on the web) and am trying to gage interest. I was thinking about a once a week format covering headlines for both large pharma and small biotechs including new approvals, development news, and the FDA. I may also give my opinion on certain topics of current interest to the industry.

As a consultant in the pharmaceutical, biotech, and fine chemicals industries, I already keep up to date on these sorts of issues anyway so I though others might find it useful. However, before I commit to this, I’d like to know what others think. If this is something people would find useful, please drop me an email using the link below in this post and let me know that you are interested. If you have any comments or suggestions for what you would like to see in such a podcast, please send them to me.

Technorati Tags: podcast

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The Baltimore Sun today reports that Lester Crawford has indeed admitted to circumventing the normal drug approval process when he unilaterally decided to delay any decision regarding Plan B.

FDA chief took over Plan B - baltimoresun.com

The article also quote Steve Galson as again saying:

Galson, who heads the FDA’s drug evaluation division, said he “saw a clear path to approve” Plan B, but Crawford expressed concern and said “he was going to make the decision on what to do with the application.”

Another quote also says he recommended approval based on the science:

Galson said he recommended approval, and there was no scientific basis for Crawford’s decision. Galson told Woodcock that Crawford might have been acting under pressure from Congress, the Bush administration or both, Woodcock testified

But the revelation that Crawford made the decision on his own as confirmed by his lawyer is definitely the most interesting fact.

Barbara van Gelder, Crawford’s lawyer, said he confirmed yesterday in his deposition for the suit that Plan B “was his decision.”

I think maybe Lester Crawford saw the writing on the wall after making this questionable decision.

This appears to be a major reason Amercans are less confident in FDA.

Technorati Tags: FDA, plan B

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A lot can change in two years. Two years ago, 56% of people thought the FDA did a good or excellent job regarding drug safety and efficacy. Now, a new poll by the Wall Street Journal Online and Harris Interactive shows that 58% feel the FDA does a poor to fair job on drug safety. It should be noted that this was conducted online from May 12-16 and so I am always cautious with online studies. This is because those online are not always representative of the public at large (although it’s not as bad as it use to be).

WSJ.com - Americans Growing Less Confident In FDA’s Job on Safety, Poll Shows (free)

The whole study is online and worth going through. A more disturbing (but perhaps insightful) number is that 82% of the people interviewed thought the process was guided more by politics than by science. Even more depressing is that only 9% thougth the FDA was influenced to a minor extent or not at all influenced by politics.

If you want to see why that may be the case, read my post on State of the Pharmaceutical Industry.

Looks like the FDA has a lot of reputation building to do with the public to restore confidence.

Technorati Tags: FDA

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According to a report out today from MSNBC, some officials at the FDA were left out of the decision regarding plan B.

MSNBC report: Top FDA staff left out of contraceptive ruling

Seems both Steve Glason director of CDER and Janet Woodcock deputy FDA commissioner were not involved in the decision and it seems to have come from Lester Crawford then FDA commissioner. Woodcock stated that she was informed of the decision rather then being involved in the process.

I find Steve Galson’s comments strange when he was the one who actually issued the written statement. He acknowledged at the time there was dissent but that it was made on scientific evidence. Here is a quote from the SF Chronicle:

In an internal memo, Galson acknowleged that “some staff have expressed the concern that this decision is based on nonmedical implications of teenage sexual behavior, or judgments about the propriety of this activity.” He called the staff’s concerns unfounded.

Now it seems he has a different story according to the MSNBC story:

Dr. Steven Galson, director of the FDA’s Center for Drug Evaluation and Research, testified that around January 2005 he was leaning toward approving Barr’s plan to sell Plan B over the counter. But then-Acting FDA Commissioner Lester Crawford “told me that he was concerned about where we were heading because he knew that I was heading towards this recommendation, and he told me that he was going to make the decision on what to do with the application,” Galson said, according to deposition transcription.

Is it just me or does this seem to be contradictory? The story surrounding plan B gets stranger and stranger.

In a Washington Post article in May 2004, Steven Galson stated:

“The decision I made had to do with looking at all the data and reading all the transcripts,” said Galson, who was named deputy director of the FDA’s drug evaluation office in 2002 after more than 10 years with other federal agencies. He said he was especially concerned about the lack of information about “the younger age group between 11 and 14, where we know there is a substantial amount of sexual activity.”

But now in the MSNBC report he states:

Galson, a doctor and career scientist who has worked at the FDA since 2001, said he had never before had his authority to make a decision removed by a commissioner.

Did he make the decision himself as he states in the Washington Post in May 2004 or did Lester Crawford make the decision for him as he now states in this MSNBC article in May 2006?

Other resources:
• San Francisco Chronical: Experts not behind reversal on Plan B / FDA bowed to politics, critics say
• Washington Post article from May 2004: FDA: Plan B Sales Rejected Against Advice

Technorati Tags: FDA, plan B

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I have posted a spreadsheet which will help in the initial evaluation of explosive hazards for chemicals. Here is the page where it is located.

This is from a paper by E. S. Shanley and G. A. Melhem of Arthur D. Little, Inc., entitled “The Oxygen Balance Criterion For Thermal Hazards Assessment“. Originally published in Process Safety Progress Volume 14, Issue 1 , Pages 29 - 31 Published Online: 17 Jun 2004

Here is the equation:
Oxygen balance = [1600 * (2x + (y/2) - z)] / M

Where:

M = molecular weight
x = number of carbon atoms
y = number of hydrogen atoms
z = number of oxygen atoms
(other heteroatoms are ignored)

If M (oxygen balance) is between -80 to +120 then the hazard potential is high
If M is +240 to +120 or -160 to -80 then the hazard potential is medium
If M is > +240 or is < -160 then the hazard potential is low.

An example: anisole C7H8O1 MW: 108.14

oxygen balance = [1600 * (2 * 7 + ( 8 / 2 ) - 1 ] / 108.14
oxygen balance = [1600 * ( 14 + 4 - 1 ) ] / 108.14
oxygen balance = [1600 * 17 ] / 108.14
oxygen balance = 27200 / 108.14
oxygen balance = + 252 therefore it isn’t a thermal hazard since it is > +240

The spreadsheet allows you to enter the molecule’s molecular weight and number of carbons, hydrogens and oxygens in it and the spreadsheet will then calculate the oxygen balance and color code the result. Below is a screenshot.

If the number is medium the result cell turns yellow; if it is high, the cell will turn red. This gives a visual feedback in addition to the number itself.

This is by no means a substitute for actual testing, but can give you a rough idea of the potential explosive hazard. The authors state that it is conceptually flawed and often dangerously misleading as a guide to energy release in general since it is based on stoichimetery. To fully answer such questions, you need to use thermochemical and kinetic considerations.

Technorati Tags: thermal hazard

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